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Background: Zishen Yutai Pill exhibited clinical benefit to infertile women undergoing fresh embryo transfer cycles, improving their pregnancy outcomes. However, as the endometrial environment in frozen embryo transfer (FET) is different from fresh cycles, the effects of ZYP on fresh embryo transfer could not be generalized to FET., Objective: We aimed to explore the effects of ZYP on live birth rate in women's FET cycles., Methods: This multicentre, double-blind, placebo-controlled, randomized study was conducted at 11 reproductive medical centres in China. Women were recruited and randomly assigned to ZYP or placebo intervention (5 g once, 3 times per day) around the time of FET. The live birth rate was set as the primary outcome. Secondary outcomes included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, pregnancy loss rates. Data was analyzed based on the intention-to-treat principle, with per protocol analysis as sensitivity analysis., Results: Between December 2017 and April 2019, 934 women were screened, of whom 880 met all eligibility criteria and were allocated to ZYP (n=441) or placebo (n=439). In ITT analysis, the live birth rates were 38.32% (169/441) in ZYP group and 32.57% (143/439) (absolute difference 5.75%, 95%CI [-0.57%, 12.00%], OR 1.29, 95%CI [0.98, 1.70], P=0.08). The intervention of ZYP did not result in significantly differences in all secondary outcomes compared with placebo (all P>0.05). Similar trends were observed in PP analysis. In post hoc analysis, ZYP resulted in higher rates of live birth than placebo among women in specific subgroups, i.e., with miscarriage history (39.23% vs. 26.45%, P=0.01) or advanced maternal age (33.93% vs. 21.85%, P=0.04)., Conclusion: In infertile women undergoing FET cycle, intervention with ZYP led to a trend of live birth rate increment compared with placebo, but without statistical significance. However, women with miscarriage history and advanced age could experience possible benefits from ZYP intervention., Registration: ChiCTR-INR-17010809 (http://www.chictr.org.cn)., Competing Interests: Declaration of competing interest This study was supported by the Guangdong Provincial Bureau of Traditional Chinese Medicine (Grant No. 20174002), Guangzhou International Science and Technology Cooperation Project (Grant No. 201807010044). Guangzhou Baiyunshan Zhongyi Pharmaceutical Co. Ltd. donated the study drugs, including Zishen Yutai Pill and the placebo for this research, but had no role in the data acquisition, statistical analysis and writing of this article. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Obesity and adverse lipid profile leads to female infertility. The cardiometabolic index (CMI) is a promising indicator for predicting obesity-related diseases. The correlation between CMI and female infertility merits further investigation., Methods: The data for this study were acquired from the 2013-2020 National Health and Nutrition Examination Survey (NHANES), with 2333 women enrolled. The cardiometabolic index (CMI) of each participant was calculated as the ratio of triglycerides and high-density lipoprotein cholesterol multiplied by waist-to-height ratio. Weighted multivariate logistic regression models were used to assess the independent correlation between the log-transformed CMI and infertility. Subgroup analyses were carried out to assess the reliability of the findings. Interaction tests were employed to determine whether variables affected infertility by interacting with log CMI., Results: A total of 2333 participants aged 18-45 years were enrolled, 274 of whom were infertile. Log CMI of the infertility group was significantly higher than that of the non-infertility group (P < 0.001). After adjustment for potential confounders, women with higher CMI were at an increased risk of infertility (OR = 2.411, 95% CI: 1.416-4.112), and this correlation was still consistent in subgroups aged under 35 years (P < 0.001). Furthermore, restricted cubic spline analysis showed a positive non-linear relationship between log CMI and infertility., Conclusions: Cardiometabolic index levels are positively correlated with increased risk of infertility in American females. Our study demonstrates the predictive capacity of CMI for female infertility., Competing Interests: Declarations Consent for publication Not applicable. Competing interests The authors declare no competing interests. Ethics approval and consent to participate All data obtained from NHANES were reviewed and approved by National Center for Health Statistics (NCHS) Ethics Review Board and all participants agreed on the survey and signed written consent. The NHANES was conducted in compliance with local laws and institutional guidelines. Since NHANES is a publicly accessible database, no additional ethical approvals are required., (© 2024. The Author(s).)

Background: Frozen embryo transfer (FET) is usually recommended for women with polycystic ovary syndrome (PCOS) undergoing In vitro fertilization (IVF). While there is no consensus as to the optimal protocol of endometrial preparation for FET. The effect of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment for FET among women with PCOS remains controversial., Purpose: We intend to explore whether GnRH-a pretreatment could improve clinical outcomes for women with PCOS undergoing FET., Methods: PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Web of Science were searched up to May 16, 2024. Eligible studies involved patients with PCOS undergoing FET and receiving GnRH-a pretreatment for endometrial preparation, with artificial cycle (AC) as the control therapy. Only randomized controlled trials (RCTs) published in Chinese and English were included. Data extraction was performed independently by two authors. Effect was quantified using odd ratios (ORs) with 95% confidence intervals (CIs) using random-effect models with the Mantel-Hansel (M-H) method in Revman software. Quality of outcomes was evaluated using the GRADEpro system. Primary outcomes contained the clinical pregnancy rate, miscarriage rate, and live birth rate. Secondary outcomes included the incidence of preterm labor and gestational diabetes mellitus (GDM)., Results: Ninety-seven records were initially retrieved, with 21 duplicates and 65 articles excluded after title and abstract screening. Seven studies were excluded due to retrospective design, leaving three RCTs with 709 participants. Among them, 353 received GnRH-a pretreatment as the intervention group and 356 received AC as the control group. No significant differences were observed in the clinical pregnancy rate (OR 1.09, 95% CI 0.75 to 1.56, P = 0.66), miscarriage rate (OR 0.73, 95% CI 0.28 to 1.90, P = 0.52), live birth rate (OR 0.87, 95% CI 0.61 to 1.25, P = 0.46), and the risk of preterm labor (OR 1.45, 95% CI 0.79 to 2.65, P = 0.23) and GDM (OR 0.73, 95% CI 0.37 to 1.48, P = 0.39) between the two groups., Conclusions: In this meta-analysis, GnRH-a pretreatment does not confer any advantages and appears unnecessary for women with PCOS undergoing FET. Additional RCTs should focus on maternal complications and the health of offspring., (© 2024. The Author(s).)

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients., Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb., Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4., Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment., (© 2024 John Wiley & Sons Ltd.)

Sexually transmitted infection is a frequent cause of tubal factor abnormality. Chlamydia trachomatis is a common causative organism for sexually transmitted infection. There are studies indicating association of chlamydial antibodies in serum with tubal abnormalities. In many centers chlamydial antibody test is done as part of routine work up for infertility. The objective of the study was to evaluate the sensitivity and specificity of chlamydial antibody test in screening infertile women for tubal factor infertility. This cross-sectional observational study was performed for one year from January 2019 to December 2019 in the Department of Reproductive Endocrinology and Infertility of Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. The infertile women having laparoscopy as part of infertility work up were enrolled in the study. The women had their serum tested for chlamydial antibody IgG by enzyme linked immune-sorbent assay. The sero-positivity for chlamydial antibody was tested against the findings of laparoscopy and dye test as gold standard for diagnosing tubal factor infertility. Statistical analysis was done to find out the sensitivity and specificity of the chlamydial antibody test in screening infertile women for tubal factor infertility. The study population included 163 infertile women with mean age 29.8±5.8 years. The tubal factor infertility was present in 56.4% of the women. The sero-positivity of Chlamydia trachomatis IgG was 36.6%. Sensitivity and specificity of Chlamydial antibody test (IgG positive) in detecting tubal factor infertility is 47.8% and 70.4% respectively. Positive predictive value of chlamydial antibody test in detecting tubal factor infertility is 41.5% and negative predictive value is 72.4%. Positive likelihood ratio is 1.59. Negative likelihood ratio is 0.74. Accuracy is 57.67%. In conclusion, the chlamydial antibody test may not be an appropriate screening test for tubal factor infertility in women of Bangladesh because of low sensitivity and moderately high specificity.

Objective: To investigate the impact of endometriosis on the therapeutic effect of hysteroscopic fallopian tube catheterization combined with laparoscopy in infertile patients with proximal tubal obstruction., Methods: We conducted a retrospective analysis of patients who underwent hysteroscopic fallopian tube catheterization combined with laparoscopy for infertility caused by proximal fallopian tube obstruction between January 19, 2016 and March 20, 2020 at the Department of Reproductive Endocrinology, West China Second Hospital, Sichuan University. During the operation, hydrotubation was performed to verify whether there was proximal tubal obstruction. Then, the patients were categorized into an endometriosis group and a non-endometriosis group according to whether their proximal tubal obstruction was combined with endometriosis. The baseline data were balanced by propensity score matching and the rate of successful surgical unblocking of proximal tubal obstruction in infertile patients by hysteroscopic fallopian tube catheterization combined with laparoscopy was calculated. Treating cases lost to follow-up in both groups as non-pregnant cases according to the principle of intention-to-treat analysis, we followed up the pregnancy outcomes after surgery. The primary indicators included overall successful surgical unblocking rate, clinical pregnancy rate, and spontaneous pregnancy rate, while the secondary indicators included live birth rate, miscarriage rate, ectopic pregnancy rate, and the mean time to spontaneous pregnancy after surgery. The primary indicators included overall successful surgical unblocking rate, clinical pregnancy rate, and spontaneous conception rate, while the secondary indicators included live birth rate, miscarriage rate, ectopic pregnancy rate, and the mean time to spontaneous pregnancy after surgery., Results: After propensity score matching, 113 cases were included in each of the two groups, with the overall successful surgical unblocking rate being 72.6%. The successful surgical unblocking rate of patients in the endometriosis group was higher than that of the non-endometriosis group, with the difference being statistically significant (78.8% vs. 66.4%, P <0.05). A total of 38 patients were lost after follow-up matching. Postoperative follow-up was performed to date and, through intention-to-treat analysis, the spontaneous conception rate was found to be higher in the endometriosis group than that in the non-endometriosis group (44.2% vs. 30.1%, P <0.05), while the mean time to spontaneous pregnancy after surgery was shorter in the endometriosis group than that in the non-endometriosis group (46 months vs. 53 months, P <0.05). There was no significant difference in clinical pregnancy rate, live birth rate, miscarriage rate, and ectopic pregnancy rate between the endometriosis group and the non-endometriosis group ( P >0.05)., Conclusion: When infertility caused by proximal tubal obstruction is combined with endometriosis, performing hysteroscopic fallopian tube catheterization combined with laparoscopy contributes to the improvement of reproduction outcomes., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Weight management is central to the treatment of infertile women with polycystic ovary syndrome. Both body mass index and waist circumference are measures of obesity. The objective of the study was to examine the clinical importance of waist circumference and body mass index in predicting insulin resistance. The cross-sectional study involved a total of 126 consecutive infertile women with polycystic ovary syndrome attending the Infertility unit of the Department of Obstetrics and Gynaecology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to December 2017. The anthropometric measurements like weight, height and waist circumference were made and body mass index and waist hip ratio were calculated. Fasting insulin and fasting plasma glucose were estimated in early follicular phase of menstrual cycle. Insulin resistance was calculated with HOMA-IR. Body mass index and waist circumference were examined for clinical prediction of insulin resistance by ROC curve analysis. The mean age was 25.56±3.90 years. Mean body mass index was 26.79±3.25, mean waist circumference was 90.9±9.4cm. By body mass index thresholds, 47.9% of the women were overweight, 39.7% of the women were obese. By waist circumference threshold, 80.2% of the women were centrally obese. Body mass index and waist circumference, both had significant correlation with hyperinsuliaemia. When body mass index and waist circumference were examined for predicting insulin resistance by sensitivity, specificity, positive likelihood ratio and negative likelihood ratio, waist circumference appeared to have moderate clinical importance compared to the negligible role of body mass index. Waist circumference may be a better predictor of insulin resistance than body mass index in infertile women with polycystic ovary syndrome.

Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-ĸB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-ĸB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIĸBα/IĸBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIĸBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-ĸB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primary ovarian insufficiency (POI) is among the foremost causes of women infertility due to premature partial or total loss of ovarian function. Resistant ovary syndrome (ROS) is a subtype of POI manifested as normal ovarian reserve but insensitive to gonadotropin stimulation. Inactivating variants of follicle-stimulating hormone receptor (FSHR), a class A G-protein coupled receptor, have been associated with POI and are inherited via an autosomal recessive pattern. In this study, we investigated the genetic causes of a primary infertility patient manifested as POI with ROS, and elucidated the structural and functional impact of variants of uncertain significance. Next-generation sequencing (NGS) combined with Sanger sequencing revealed novel compound heterozygous FSHR variants: c.1384G>C/p.Ala462Pro and c.1862C>T/p.Ala621Val, inherited from her father and mother, respectively. The two altered amino acid sequences, localized in the third and seventh transmembrane helix of FSHR, were predicted as deleterious by in silico prediction. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression. In conclusion, two unreported inactivating FSHR variants potentially responsible for POI with ROS were first identified. This study expands the current phenotypic and genotypic spectrum of POI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Chen, Wang, Shu, Zhou, Wu, Jin, Yang, Sun, Qi and Shu.)

Objective: The purpose of this study was to explore the association of expression of cystic fibrosis transmembrane conductance regulator (CFTR) in cumulus cells (CCs) from mature oocytes with oocyte quality and embryonic development., Methods: A total of 338 infertile women who underwent ovarian stimulation cycle of oocyte retrieval in Zhejiang University School of Medicine were retrospectively enrolled in this study. The relative mRNA expression levels of CFTR, bone morphogenetic protein 15 (BMP15), and growth differentiation factor 9 (GDF9) in CCs were detected by qPCR technology. ROC curve was applied for the diagnosis of oocyte maturation. The serum levels of anti-Müllerian hormone (AMH), E 2 , follicle-stimulating hormone (FSH), luteinizing hormone (LH), and androstenedione were measured. Oocyte maturation rate, fertilization rate, cleavage rate, high-quality embryo formation rate, and implantation rate after embryo transfer were also determined., Results: The mRNA expression levels of CFTR in CCs were significantly increased in metaphase II (MII) oocytes compared to that in metaphase I (MI) or germinal vesicle (GV) oocytes. The ROC curve analysis illustrated that CFTR mRNA expression could efficiently discriminate MII oocytes from MI or GV oocytes (AUC = 0.954), and revealed that 0.695 RQU is the optimal cut-off value for diagnosis. So the cut-off value of 2 -ΔΔCT  = 0.70 was used to divide the patients into two groups: low- (n = 114) and high-CFTR group (n = 224). The mRNA expression of CFTR in CCs was positively correlated with the antral follicular count (AFC), number of oocytes retrieved, number of MII oocytes, serum E 2 level on hCG day, and BMP15 and GDF9 expression in CCs. Under continuous stimulation with the same dose of recombinant follicle-stimulating hormone (rFSH), the number of follicles, average recovered oocytes, recovered oocytes, MII oocytes, as well as the oocyte recovery rate, fertilization rate, oocyte cleavage rate, high-quality embryo formation rate, and implantation rate were decreased in patients with lower CFTR., Conclusions: This study suggests that CFTR expression in CCs is associated with the developmental potential of human oocytes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: T/Y-shaped dysmorphic uterus is frequently associated with subfertility, abortion, preterm delivery, and recurrent implantation failure. In this study, the impact of hysteroscopic metroplasty for a T/Y-shaped uterus on obstetric outcomes was investigated in patients with infertility and recurrent pregnancy loss (RPL) and compared the uterine anomaly subgroups., Method: Cases with infertility and/or RPL diagnosed with T/Y-shaped uterus by hysterosalpingography (HSG) and 3D transvaginal ultrasonography (3D TVUSG) with no other male or female pathology have recruited the study. Medical history and the obstetric outcome after two years of follow-up were recorded., Results: Out of the 92 cases recruited, T-shaped uteri (Group-1) were observed in 30, while 62 (67.3%) patients had Y-shaped uteri. Pregnancy was achieved in 50 (54.3%) of the cases, 28 (56%) of the pregnancies occurred spontaneously, and in 22 (44%) pregnancy was achieved through assisted reproductive techniques (ART). Term delivery occurred in 29 (76.3%) of the pregnancies while 9 (23.6%) had preterm deliveries and a total of 38 (76%) resulted in a live birth. Out of the 31 patients with previous RPL history, 13 (41.9%) achieved pregnancy and 11 out of 13 (84.6%) had a term pregnancy followed by live birth., Conclusion: Spontaneous pregnancy, and term pregnancy rates after surgery were found to be promising in these uterine anomalies. The pregnancy outcome of the primary infertile patients was found the same in two groups (50%-46.1%), but the results of the RPL patients were found to be better in the T-shaped group than in the Y-shaped group (70%-28.5%).

The aim of this study was to compare the reproductive outcomes between infertile women who underwent hysteroscopic uterine septum resection and those who required a second look hysteroscopy due to residual septum prior to intracytoplasmic sperm injection (ICSI) cycles with selective single 'Grade A' embryo transfer (ET). All second look hysteroscopies were performed due to partial remnant septum in a control three dimensional transvaginal ultrasonography (3D TVUSG) after the first hysteroscopic resection. Miscarriage and biochemical pregnancy rates were not different between the groups while clinical pregnancy and live birth rates were significantly higher in Group 2 than in Group 1. Second look hysteroscopic metroplasty performed to restore remnant septum significantly improves live birth rate as well as clinical pregnancy rates while it appears not to alleviate abortion and biochemical pregnancy rates in women undergoing ICSI-ET.IMPACT STATEMENT What is already known on this subject? The effect of hysteroscopic septum resection on reproductive outcomes in IVF treatment in infertile patients with uterine septum is not clearly known. What do the results of this study add? With the selective single ET strategy, complete or partial hysteroscopic correction of the uterine septum before ICSI and subsequent resection of the residual septum with control hysteroscopy significantly increases the live birth rates in the infertile population. What are the implications of these findings for clinical practice and/or further research? In the group of infertile patients with uterine septum, second control hysteroscopy should be performed 1 month later for residual septum or adhesions after hysteroscopic septum resection performed once.

Decidualization is an essential process for embryo implantation and maintenance of pregnancy, and abnormal decidualization contributed to several pregnancy disorders like a miscarriage. The objective of this study was to explore the regulation and function of CD55 in human decidualization. By immunohistochemical staining, it was found that CD55 expression was higher in first-trimester decidua than in the endometrium. In both primary endometrial stromal cells and immortalized cell line T-hESCs, CD55 was upregulated by induction of in vitro decidualization with medroxyprogesterone acetate (MPA) and 8-Br-cAMP. During decidualization in vitro, CD55 was stimulated by 8-Br-cAMP in a time- and concentration-dependent manner, which was reversed by a PKA inhibitor H89 and partially by an AKT activator SC79. Knocking down CD55 expression diminished the expression of decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1), accompanied by inhibition of Src, aberrant activation of ERK and decreased expression of several decidualization-related genes, including FOXO1, EGFR, and STAT3. Furthermore, the decidua of unexplained miscarriage women and the endometrium of unexplained infertile women both exhibited decreased CD55 expression. Collectively, these findings revealed that 8-Br-cAMP promotes CD55 expression via PKA activation and AKT dephosphorylation, and decreased CD55 impairs decidualization by inactivation of Src, aberrant activation of ERK pathway, and compromised expression of decidualization-related genes, indicating that CD55 deficiency may contribute to the pathogenesis of spontaneous miscarriage and infertility., (© 2022 Wiley Periodicals LLC.)

Objective: To evaluate the psychological domain of quality of life (PDQoL), anxiety and depression levels of infertile women with endometriosis versus non endometriosis who applied for Assisted Reproductive Technologies (ART)., Method: This prospective case-control study compromised a total of 105 women who applied for IVF/ICSI program. Ninety-three women were divided into two groups as endometriosis ( n  = 37) and non-endometriosis ( n  = 56) after 12 patients who refused to participate in the study were excluded. The WHOQOL-BREF questionnaire, Beck Depression and Anxiety Inventory scales were used to determine the psychological stress levels., Results: A significant difference was found between the endometriosis and non-endometriosis groups regarding depression scores, while no significant difference was reported with respect to PDQoL and anxiety ( p  < 0.01, p  = 0.897 and p  = 0.058, respectively). A weak but significant correlation was observed between depression and endometriosis (CC: 0.435, p  < 0.01). Though anxiety scores were found to be higher in endometriosis group this can not reach statistical significance ( p  = 0.058). Impact of PDQoL, depression and anxiety scores on pregnancy outcomes were found to be insignificant., Conclusion: Women with endometriosis seem to be more susceptible to depression and anxiety than women without endometriosis. Although infertility treatment outcomes are not found to be significantly affected, the impact of depression and anxiety over ART treatment success merit further research.

We aimed to compare the efficacy of two different starting doses of recombinant follicle stimulating hormone (rFSH), 37.5 vs. 75 international units (IU) for intrauterine insemination (IUI) cycles in non-obese women with polycystic ovary syndrome (PCOS). A total of 109 women who underwent first rFSH stimulated IUI cycle were included in this retrospective cohort study. The primary outcome measure was the clinical pregnancy rate. No significant difference was found in terms of clinical pregnancy rate between the two groups (22% for the 37.5-IU group and 24% for the 75-IU group, respectively, p  = .808). There was no significant difference in monofollicular development rate among the groups ( p  = .354). The total rFSH consumption was lower in the 37.5-IU group compared to the 75-IU group ( p < .001). There was no statistically significant difference in pregnancy rates between the 37.5-IU and 75-IU groups in both normal weight (BMI: 19-24.9 kg/m 2 ) and overweight (BMI: 25-29.9 kg/m 2 ) women ( p  = .889 and .518, respectively). These results suggest that the starting doses of 37.5 and 75 IU of rFSH do not show significant difference in clinical pregnancy rates in non-obese PCOS women undergoing IUI cycles.Impact Statement What is already known on this subject? Low-dose gonadotropin treatment is advised for women with polycystic ovary syndrome (PCOS). However, there are few comparative data on the efficacy of different starting doses of recombinant follicle stimulating hormone (rFSH) for intrauterine insemination (IUI) cycles in PCOS women. What the results of this study add? There was no statistically significant difference in pregnancy rates of non-obese patients with PCOS having IUI whether rFSH was started at 37.5 or 75 international units (IU). What the implications are of these findings for clinical practice and/or further research? A starting dose of 37.5 IU of rFSH may be a reasonable approach for IUI cycles in non-obese PCOS women.

Controlled ovarian hyperstimulation (COH) is the most common therapeutic protocol to obtain a considerable number of oocytes in IVF-ET cycles. To date, the risk factors affecting COH outcomes remain elusive. Growth differentiation factor 8 (GDF-8), a member of transforming growth factor β (TGF-β) superfamily, has been long discerned as a crucial growth factor in folliculogenesis, and the aberrant expression of GDF-8 is closely correlated with the reproductive diseases. However, less is known about the level of GDF-8 in IVF-ET patients with different ovarian response. In the present study, the potential risk factors correlated with ovarian response were explored using logistic regression analysis methods. Meanwhile, the expression changes of GDF-8 and its responsible cellular receptors in various ovarian response patients were determined. Our results showed that several factors were intensely related to poor ovarian response (POR), including aging, obesity, endometriosis, surgery history, and IVF treatment, while irregular menstrual cycles and PCOS contribute to hyperovarian response (HOR). Furthermore, POR patients exhibited a decrease in numbers of MII oocytes and available embryos, thereby manifesting a lower clinical pregnancy rate. The levels of GDF-8, ALK5, and ACVR2B in POR patients were higher compared with those in control groups, whereas the expression level of ACVR2A decreased in poor ovarian response patients. In addition, clinical correlation analysis results showed that the concentration of GDF-8 was negatively correlated with LH and estradiol concentration and antral follicle count. Collectively, our observations provide a novel insight of ovarian response-associated risk factors, highlighting the potential role of GDF-8 levels in ovarian response during COH process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bai, Pan, Zhao, Chen, Xiang, Yang and Zhu.)

A 31-year-old woman, who had been diagnosed with craniopharyngioma (CP) at the age of 13, suffered secondary hypopituitarism after two surgical resections of CP, receiving supplement of levothyroxine, cortisone, and sequential estrogen and progesterone because of primary amenorrhea. She managed to conceive after ovulation induction with human menopausal gonadotropin. Luteal phase deficiency (LPD) was found during the first trimester, as the progesterone stayed at a low level between 0.07 and 1.63 ng/ml within seven gestational weeks, followed by a gradual rise from 4.01 up to 34.70 ng/ml in the 11th week, which was mainly secreted by the placenta. Estrogen and progesterone were administered to the patient as luteal support until the 12th week, who succeeded in delivering a healthy baby at term. In conclusion, the patient with hypopituitarism who develops severe LPD during the early pregnancy may need luteal support until 12th week., (© 2021 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Objective: To identify predictors of the ovarian response to clomiphene citrate (CC) in infertile patients with polycystic ovary syndrome (PCOS)., Methods: We performed a prospective cohort study of infertile patients with PCOS. The participants underwent assessments of their physical, endocrine, and metabolic characteristics, and treatment with CC at an initial dose of 50 mg/day and a maximum of 100 mg/day between days 3 and 7 of their menstrual cycles. Participants who ovulated were identified as responders and those who did not as non-responders., Results: Of the 72 participants, 48 (66.7%) were identified as responders and 24 as non-responders. Sex hormone-binding globulin (SHBG) (odds ratio 1.022, 95% confidence interval: 1.000-1.045) was found to be associated with the ovarian response to CC using logistic multivariate regression analysis. Receiver operating characteristic analysis also showed that SHBG was a significant predictor of the response to CC (area under the curve 0.799)., Conclusion: We have shown that SHBG is the best prognostic indicator of an ovulatory response to CC. However, larger prospective studies, in which more variables are assessed, are required to confirm this finding and to identify appropriate cut-off values.

Aim: Endometriosis, one of the most common gynecological disorder, is a challenging disease observed in 20 %-40 % of subfertile women. Endometriomas affect 17-44 % of women with endometriosis. Because endometrioma has detrimental effects on fertility, many of these women need Assisted Reproductive Technology (ART) to conceive. In this study, we aimed to investigate the effects of endometrioma presence and impact of bilaterality over In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) outcomes., Method: The study was designed retrospectively. A total of 159 women enrolled in IVF / ICSI cycles were included. Patients were divided into two groups as Endometrioma group (n: 73) and control group (n:86). In Endometrioma group, subgroup analysis was performed according to whether endometrioma was unilateral or bilateral. Demographic characters, clinical and laboratory parameters were recorded. SPSS was used for analysis., Results: In endometrioma group, although basal FSH levels was higher than control group, it was within normal limits, while estradiol levels was lower (p < 0.001, p 0.042, respectively). Antral follicle count (AFC), dominant follicle number, total oocyte count, MII oocyte numbers were found to be significantly lower, whereas numbers of embryos achieved, clinical pregnancy rates (PR) and live birth rates (LBR) were found to be similar.There were no statistically significant differences in terms of Antimullerian Hormon (AMH) levels, oocyte and embryo quality, the numbers of embryos achieved, PR and LBR between unilateral and bilateral endometrioma groups., Conclusion: This study shows that presence of endometrioma negatively effects fertility parameters albeit no significant effect over embryo quality, PR and LBR whereas bilaterality doesn't have any influence over any fertility parameters and PR., Competing Interests: Declaration of Competing Interest All of the authors of this manuscript declare that they have no conflicts of interest, (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The "central dogma" of molecular biology, that is, that DNA blueprints encode messenger RNAs which are destined for translation into protein, has been challenged in recent decades. In actuality, a significant portion of the genome encodes transcripts that are transcribed into functional RNA. These noncoding RNAs (ncRNAs), which are not transcribed into protein, play critical roles in a wide variety of biological processes. A growing body of evidence derived from mouse models and human data demonstrates that ncRNAs are dysregulated in various reproductive pathologies, and that their expression is essential for female gametogenesis and fertility. Yet in many instances it is unclear how dysregulation of ncRNA expression leads to a disease process. In this review, we highlight new observations regarding the roles of ncRNAs in the pathogenesis of disordered female steroid hormone production and disease, with an emphasis on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). We will focus our discussion in the context of three ovarian disorders which are characterized in part by altered steroid hormone biology - diminished ovarian reserve, premature ovarian insufficiency, and polycystic ovary syndrome. We will also discuss the limitations and challenges faced in studying noncoding RNAs and sex steroid hormone production. An enhanced understanding of the role of ncRNAs in sex hormone regulatory networks is essential in order to advance the development of potential diagnostic markers and therapeutic targets for diseases, including those in reproductive health. Our deepened understanding of ncRNAs has the potential to uncover new applications and therapies; however, in many cases, the next steps will involve distinguishing critical ncRNAs from those which are merely changing in response to a particular disease state, or which are altogether unrelated to disease pathophysiology., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Study Question: Does follicular flushing increase the number of mature oocytes in monofollicular IVF?, Summary Answer: Follicular flushing increases the number of mature oocytes in monofollicular IVF., What Is Known Already: Flushing increases neither the oocyte yield nor the pregnancy rate in polyfollicular IVF or in poor responder patients. In monofollicular IVF, the effect of flushing has so far been addressed by two studies: (i) a prospective study with minimal stimulation IVF demonstrated an increased oocyte yield, and (ii) a retrospective study with natural cycle (NC)-IVF showed an increased oocyte yield and an increased transfer rate., Study Design, Size, Duration: Randomized controlled trial including 164 women who were randomized for either aspiration with or without flushing from 2016 to 2019., Participants/materials, Setting, Methods: Infertile women 18-42 years of age with an indication for IVF treatment at a university-based infertility unit. Women undergoing monofollicular IVF were randomized to either follicular aspiration only or follicular aspiration directly followed by five follicular flushes at a 1:1 ratio. The intervention was done without anaesthesia, using a gauge 19 single-lumen needle. Flushing volume was calculated (sphere formula) based on the size of the follicle., Main Results and the Role of Chance: A total of 164 women were included; 81 were allocated to 'aspiration only' and 83 to additional 'flushing'. Primary analysis was based on the intention-to-treat: oocyte yield, defined as the collected mature oocyte rate, was higher (n = 64/83, 77.1%) in the flushing group compared to the aspiration only group (n = 48/81, 59.3%, adjusted risk difference (RD): 18.2% (95% CI 3.9-31.7%), P-value = 0.02). In the flushing group, most oocytes were retrieved within the first three flushes (63/83, 75.8%). Fertilization rate was higher in the flushing group (n = 53/83, 63.9% vs n = 38/81, 46.9%; adjusted RD: 16.8% (96% CI 1.5-31.4%), P = 0.045). Transfer rate was also higher in the flushing group (n = 52/83, 62.7% vs n = 38/81, 46.9%; RD: 15.71 (95% CI 0.3-30.3%)), but the difference was not significant (P = 0.06). The clinical pregnancy rate n = 9/83 versus n = 9/81 (RD: -0.3% (95% CI -9.9% to 9.5%)) and live birth rate n = 7/83 versus n = 8/81 (RD: -1.5% (95% CI -10.4% to 7.1%)) were not significantly different between the flushing and the aspiration group. The median duration of the intervention was significantly longer with flushing (2.38 min; quartiles 2.0, 2.7) versus aspiration only (0.43 min; quartiles 0.3, 0.5) (P < 0.01). There was no significant difference in the mean (±SD) visual analogue scales pain score between the follicular flushing (3.4 ± 1.8) and the aspiration group (3.1 ± 1.89)., Limitations, Reasons for Caution: Blinding of the procedure was not possible., Wider Implications of the Findings: Our study proved that flushing of single follicles in NC-IVF increases the oocyte yield. In contrast to polyfollicular IVF flushing seems to be beneficial in a monofollicular setting if the technique used in our study (single-lumen needle, 5 flushings with flushing volume adaptation) is applied., Study Funding/competing Interest(s): The study was funded by the financial sources of the division and in part by a research grant provided by NMS Biomedical SA, Switzerland. The company did not have any roles in design or conduct of the study or in the preparation of the manuscript. The authors have no other conflicts of interest., Trial Registration Number: Clinicaltrials.gov NCT02641808., Trial Registration Date: 29 December 2015., Date of First Patient’s Enrolment: 22 August 2016., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Purpose: To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield., Methods: Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p < 0.05)., Results: Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = - 0.45, biologic age Pearson ρ = - 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (- 6.9 oocytes (CI - 11.6, - 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (- 3.1; 95% CI - 6.5, - 0.1; p = 0.036)., Conclusions: In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.

Study Question: Can cytochrome P450 oxidoreductase deficiency (PORD) be revealed in adult women with menstrual disorders and/or infertility?, Summary Answer: PORD was biologically and genetically confirmed in five adult women with chronically elevated serum progesterone (P) who were referred for oligo-/amenorrhea and/or infertility., What Is Known Already: PORD is an autosomal recessive disease typically diagnosed in neonates and children with ambiguous genitalia and/or skeletal abnormalities. It is responsible for the decreased activity of several P450 enzymes, including CYP21A2, CYP17A1 and CYP19A1, that are involved in adrenal and/or gonadal steroidogenesis. Little is known about the optimal way to investigate and treat patients with adult-onset PORD., Study Design, Size, Duration: In this series, we report five adult females who were evaluated in three tertiary endocrine reproductive departments between March 2015 and September 2018., Participants/materials, Setting, Methods: Five women aged 19-38 years were referred for unexplained oligo-/amenorrhea and/or infertility. Genetic testing excluded 21-hydroxylase deficiency (21OH-D), initially suspected due to the increased 17-hydroxyprogesterone (17-OHP) levels. Extensive phenotyping, steroid profiling by mass spectrometry, pelvic imaging and next-generation sequencing of 84 genes involved in gonadal and adrenal disorders were performed in all patients. IVF followed by frozen embryo transfer (ET) under glucocorticoid suppression therapy was performed for two patients., Main Results and the Role of Chance: All patients had oligomenorrhea or amenorrhea. None had hyperandrogenism. Low-normal serum estradiol (E2) and testosterone levels contrasted with chronically increased serum P and 17-OHP levels, which further increased after adrenocorticotrophic hormone (ACTH) administration. Despite excessive P, 17OH-P and 21-deoxycortisol rise after ACTH stimulation suggesting non-classic 21OH-D, CYP21A2 sequencing did not support this hypothesis. Basal serum cortisol levels were low to normal, with inadequate response to ACTH in some women, suggesting partial adrenal insufficiency. All patients harbored rare biallelic POR mutations classified as pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics standards. Pelvic imaging revealed bilateral ovarian macrocysts in all women. IVF was performed for two women after retrieval of a normal oocyte number despite very low E2 levels during ovarian stimulation. Frozen ET under glucocorticoid suppression therapy led to successful pregnancies., Limitations, Reasons for Caution: The number of patients described here is limited and these data need to be confirmed on a larger number of women with non-classic PORD., Wider Implications of the Findings: The diagnosis of PORD must be considered in infertile women with chronically elevated P and 17OH-P levels and ovarian macrocysts. Differentiation of this entity from non-classic 21OH-D is important, as the multiple enzyme deficiency requires a specific management. Successful fertility induction is possible by IVF, providing that P levels be sufficiently suppressed by glucocorticoid therapy prior to implantation., Study Funding/competing Interest(s): No specific funding was used for this study. There are no potential conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare incidence, risk factors, and etiology of women's deaths in fertile, subfertile, and undergoing assisted reproductive technology (ART) in the years after delivery., Design: Retrospective cohort., Setting: University hospital., Patient(s): Women who had delivered in Massachusetts., Intervention(s): This study used data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System linked to vital records, hospital stays, and the Massachusetts death file. Mortality of patients delivered from 2004-2013 was evaluated through 2015. The exposure groups, determined on the basis of the last delivery, were ART-treated (linked to Society for Assisted Reproductive Technology Clinic Outcome Reporting System), subfertile (no ART but with indicators of subfertility including birth certificate checkbox for fertility treatment, prior hospitalization for infertility [International Classification of Disease codes 9 628 or V23], and/or prior delivery with checkbox or ART), or fertile (neither ART nor subfertile). Numbers (per 100,000 women-years) and causes of death were obtained from the Massachusetts death file., Main Outcome Measure(s): Mortality of women after delivery in each of the three fertility groups and the most common etiology of death in each., Result(s): We included 483,547 women: 16,429 ART, 11,696 subfertile, and 455,422 fertile among whom there were 1,280 deaths with 21.1, 25.5, and 44.7 deaths, respectively, per 100,000 women-years. External causes (violence, accidents, and poisonings) were the most common reasons for death in the fertile group. Deaths occurred on average 46 months after delivery. When external causes of death were removed, there were 19.1, 17.0, and 25.6 deaths per 100,000 women-years and leading causes of death in all groups were cancer and circulatory problems., Conclusion(s): The study presents reassuring data that death rates within 5 years of delivery in ART-treated and subfertile women do not differ from those in fertile women., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine., Objective and Rationale: The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included., Search Methods: Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217)., Outcomes: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls)., Wider Implications: For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objective: To evaluate in vitro fertilization (IVF) outcomes of proximal fallopian tube embolization by interventional radiology compared with laparoscopic salpingectomy before embryo transfer (ET) in patients with hydrosalpinx., Design: A single-center, off-label, nonrandomized prospective study., Setting: Academic university hospital., Patients: One hundred fifty-five patients with hydrosalpinx were identified on ultrasound or hysterosalpingography desiring IVF between April 2016 and December 2017., Interventions: Radiologically guided tubal occlusion with embolization microcoils (RTO-EM) and laparoscopic salpingectomy., Measurements and Main Results: Of the 155 analyzed patients, 42 were treated with RTO-EM and 113 with laparoscopic salpingectomy. The subsequent IVF outcomes, including implantation, clinical pregnancy, miscarriage, ectopic pregnancy, and ongoing pregnancy (i.e., a fetal heartbeat on ultrasound beyond 10 weeks) were compared between the 2 groups. Implantation and clinical pregnancy per ET cycle in the RTO-EM group were similar to that of the salpingectomy group (26.7% vs 30.2% [p = .51] and 39.0% vs 45.3% [p = .40], respectively), with a similar miscarriage rate. There was no statistically significant difference in ectopic pregnancies between the 2 groups. Moreover, no difference was detected in ongoing pregnancy per cycle between the 2 groups (33.9% vs 41.2%; p = .32). The ongoing-pregnancy rate per patient following RTO-EM was 47.6% (20 of 42) compared with 61.9% (70 of 113) following salpingectomy (odds ratio, 0.56; 95% confidence interval, 0.27-1.14; p = .11)., Conclusion: Pregnancy in the RTO-EM group was comparable to the salpingectomy group in patients with hydrosalpinx before ET treatment. RTO-EMs may be an alternative to salpingectomy for patients with hydrosalpinx planning for IVF-ET., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Research Question: There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF., Design: This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screening tests including human papillomavirus were normal. Immune cells were analysed using three techniques: fluorescence-activated cell sorting, immunohistochemistry and gene expression. A human leukocyte antigen (HLA)-C tetramer was used as an 'artificial embryo'. The expression of genes including those for tumour necrosis factor (TNF)-α and interleukin-10 (IL-10) was analysed., Results: A comparison was made of the percentage and gene expression of CD56 bright CD16 - uterine natural killer (uNK), CD56 dim CD16 + natural killer cells, CD56 - CD16 + natural killer cells and TregCD25 + CD4 + FoxP3 + cells, uNK binding to the HLA-C tetramer, and TNF-α and IL-10 expression. No between- or within-group differences were observed in natural versus ovarian stimulation cycles., Conclusions: Ovarian stimulation does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing ovarian stimulation. Further studies are underway to find out if different responses might be seen in women with previous autoimmune disorders., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the prevalence of female sexual dysfunction (FSD) and depression in primary infertile women with 25-Hydroxyvitamin D3 (25-OH VD) deficiency undergoing in-vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) treatment., Materials and Methods: A total of 80 women with 25-OH VD3 deficiency (<20 ng/mL = group 1), 80 women with 25-OH VD3 insufficiency (20-29.9 ng/mL = group 2), and 80 women with a normal 25-OH VD3 level (30-60 ng/mL = group 3) were included the study. Female sexual function and depression were measured using the Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI)., Results: No statistically significant differences were found among the groups in terms of demographic characteristics, baseline and laboratory parameters. Statistically significant differences were observed among the groups with regard to FSD and depression. The FSFI (group 1 = 22.46 ± 2.13, group 2 = 25.82 ± 2.13 and group 3 = 28.66 ± 2.13, respectively) and sexual domain scores were low in women with 25-OH VD deficiency, and the number of women with depression (BDI score ≥ 17) was high (p < 0.05). Correlation analysis showed that the sexual domain scores were positively correlated with the 25-OH VD level, and the BDI score showed a significant negative correlation with the total FSFI score and 25-OH VD levels., Conclusion: The 25-OH VD status was associated with FSD and depression and that the degree of sexual dysfunction could depend on the severity of 25-OH VD levels. Further studies are needed to elucidate this issue., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Research Question: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China?, Design: Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy., Results: Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy., Conclusion: The prevalence of infertility in China is high, but the uptake of treatment is relatively low., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In this study, our aim was to determine which factor is more correlated with the number of oocytes retrieved in patients with endometrioma compared with controls undergoing in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) cycles: antral follicle count (AFC) or anti-Müllerian hormone (AMH). A total of 60 women with endometrioma and a control population of 60 women without endometrioma in the same period were randomly selected underwent the injection IVF-ICSI treatment. No significant differences were found between the groups in terms of age (28.78 ± 3.49 vs. 29.52 ± 2.47, p = .187), body mass index (23.62 ± 2.05 vs. 23.91 ± 2.11, p = .449), duration of infertility [(3 (2-4) vs. 3 (2-3), p = .139)], AMH level (1.52 ± 0.51 vs. 1.32 ± 0.92, p = .133), duration of stimulation [(9 (9-10) vs. 10 (9-10), p = .135)], total gonadotropin dose [(2750 (2262.5-3337.5) vs. 2770 (2680-3562.5), p = .125)], endometrial thickness [(10 (10-11) vs. 10 (9-11), p = .463)], fertilisation rates (67.20 ± 18.04 vs. 62.28 ± 17.13, p = .123), grade I embryo (43.3% vs. 30%, p = .185), clinical pregnancy rates (40% vs. 26.7%, p = .123), and the perinatal outcomes between the groups. The AFC was higher in the controls than in those with endometrioma (9.20 ± 1.80 vs. 6.32 ± 2.04, p < .001). The number of oocytes retrieved was also higher in the controls than in those with endometrioma [(7 (6-8) vs. 4 (4-5.75), p < .001)]. We found that women with endometrioma had a significantly lower number of oocytes retrieved than the controls despite the same AMH levels in both groups. AFC is a better marker of ovarian response than AMH in women with endometrioma undergoing IVF-ICSI. Impact statement What is already known on this subject? Utilising the ovarian reserve is important in the success of ovarian stimulation and in evaluating the success of assisted reproductive technologies. The anti-Müllerian hormone (AMH) level and the antral follicle count (AFC) are widely used in the prediction of ovarian functional reserve and response. However, no perfect marker exists in the evaluation of ovarian reserve and ovarian response. What do the results of this study add? Our study demonstrated that women with endometrioma have a significantly lower number of oocytes retrieved than the controls, despite the same AMH levels in both groups; which strongly suggests that AFC is a better reflection of ovarian response than AMH in women with endometrioma undergoing an in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI). What are the implications of these findings for clinical practice and/or further research? This important issue has been reviewed and discussed for years, however, the conclusions are still controversial. Additional research is needed to understand which ovarian reserve test could better predict ovarian response outcome?

Background: To evaluate the hysterosalpingography (HSG) findings of women with infertility in a tertiary center located in central Turkey., Methods: A total of 1,996 patients undergoing the HSG procedure for the investigation of infertility from April 2012 to 2017 were retrospectively evaluated using the archives of the reproductive endocrinology and radiology departments. Demographic and clinical characteristics of patients with normal HSG findings (n = 1,549) and patients with abnormal HSG findings (n = 447) were compared, and the distribution of pathologies on the HSG examinations was evaluated as well., Results: There were statistically significant differences between patients with normal and abnormal HSG findings in terms of age (25.68 ± 4.54 vs. 35.87 ± 2.65, p < 0.001), type (for secondary) and duration of infertility [43.1% vs. 50.6% (p = 0.006); 7 (1-22) vs. 2 (1-12) (p < 0.001), respectively], and baseline follicle stimulating hormone and estradiol levels [7.22 ± 1.38 vs. 7.55 ± 1.42 (p < 0.001); 45.54 ± 9.92 vs. 44.40 ± 9.99 (p < 0.001), respectively]. Among a total of 1,996 HSG examinations, 447 (22.39%) showed abnormalities, of which 237 (11.87%) were associated with tubal pathologies, 163 (8.17%) with uterine pathologies, and 47 (2.35%) with a combination of both. While the most common tubal pathology was one-sided distal tubal occlusion (2.91%), the most common uterine pathology was filling defects (4.16%)., Conclusion: HSG is the most commonly used, well-tolerated, low-cost, and safe radiological procedure to use for the investigation of the causes of female infertility., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Female mice (Y123F) with substitution mutations introduced through homologous gene targeting, replacing the three tyrosine residues of LepR, Tyr985, Tyr1077, and Tyr1138 with phenylalanine, could induce infertility. This study aimed to describe the reproductive alteration and to explore its mechanism. We compared the reproductive characteristics in the female homozygous (HOM) Y123F mice and wild-type (WT) littermates, analyzing the expression of downstream molecules of LepR, like protein kinase B (Akt)/mammalian target of rapamycin (mTOR), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and insulin receptor substrate (IRS) in the ovaries. The results showed that 10-week old female Y123F HOM exhibited no reproductive periods, declined anti-mullerian hormone (AMH) levels in the serum and ovaries, reduced primordial follicles, primary follicles, secondary follicles, antral follicles and hardly no corpus lutea (all p < .05). The phosphorylation of downsream Akt, mTOR, S6K1 and eIF4B of LepR were all elevated in the ovaries of the mutated female mice. They also presented a decreased phosphorylation of IRS-1, IRS-2, and PTEN, and a strengthened phosphorylation of FOXO-3A in the ovaries. In conclusions, LepR mutation could result in follicle loss and activation of PTEN/PI3K/Akt/mTOR pathway in adult female mice, independent of insulin signaling pathway.

In this study, we aimed to investigate serum and follicular fluid (FF) secreted frizzle-related protein-5 (Sfrp-5) levels in nonobese, nonhyperandrogenic patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), in addition to IVF outcomes. In total, 160 patients undergoing IVF treatment were included in the study: 80 patients diagnosed with PCOS according to the Rotterdam criteria (group I, study) and 80 patients with the etiology of male factor infertility (group II, control). There were statistically significant between-group differences in serum estradiol (E 2 ) levels on the day of hCG administration (2377.00 ± 733.23 vs. 1931.3 ± 1,010.69), the total gonadotropin dose required (2000.63 ± 1,051.87 vs. 1.134.69 ± 286.45), and the total number of retrieved oocytes (8.60 ± 2.06 vs. 11.05 ± 4.39) (p < 0.05). There was also a statistically significant between-group difference in serum and FF Sfrp-5 levels on the day of oocyte retrieval (11.40 ± 2.88 vs. 8.87 ± 1.85, p < 0.001; 11.06 ± 2.30 vs. 9.71 ± 2.15, p = 0.008; respectively). However, there were no between-group differences in fertilization rates, clinical pregnancy rates, and live birth rates (p > 0.05). A correlation analysis showed that serum and FF Sfrp-5 levels were associated with insulin and inflammatory markers (p < 0.05). In a selected population of nonobese, nonhyperandrogenic PCOS patients, there was a significant difference in Sfrp-5 levels of the PCOS group versus those of the control group. Further studies are needed to determine the effects of Sfrp-5 in women with PCOS.

Objective: The aim of this meta-analysis is to explore the beneficial role of granulocyte colony-stimulating factor (G-CSF) on infertile women under artificial reproduction technology treatment., Method: Medline, Embase and ISI Web of Science databases were searched to identify relevant randomized control trials. Studies before July, 2017 were included for primary screening. Meta-analysis of the total and subgroup patients was conducted, and relative risks (RRs) and their 95% confidence intervals (95% CI) were calculated by a fixed-effect model if no heterogeneity (evaluated as I 2 statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by administrating route or clinical indication. Egger test and influence analysis were conducted to evaluate the publication bias and study power, respectively., Results: The final selection enrolled 10 RCTs, involving 1016 IVF-ET cycles (521 distributed to the G-CSF group and 495 to the control). Compared with control group, G-CSF administration could significantly improve clinical pregnancy rate (CPR, RR 1.89, 95% CI 1.53-2.33), while it had no beneficial effect on embryo implantation rate (IR, RR 1.84, 95% CI 0.84-4.03). The subgroup analysis by administration route showed that both uterine infusion and subcutaneous injection can produce a substantial increase in CPR, with the pooled RRs (95% CI) 1.46 (1.04-2.05) and 2.23 (1.68-2.95), respectively. Nevertheless, most of included RCTs dealt with the RIF subjects, and the pooled analysis of this data showed a higher PR and IR in G-CSF group as compared to that in the control, with the RRs (95% CI) 2.07 (1.64-2.61) and 1.52 (1.08-2.14), respectively. Egger regression test did not demonstrate any significance for the publication bias., Conclusion: G-CSF administration has a beneficial role on the clinical outcome after embryo transfer by both routes of local infusion and systematic administration, especially for the cases with RIF. Further RCTs are needed to investigate the role of G-CSF in thin endometrium patients.

Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women at reproductive age. Although the aetiology of PCOS remains unclear, potential effects of environmental endocrine-disrupting compounds on the development of PCOS have drawn increasing attention. The aim of the current study was to examine the association between triclosan (TCS) and PCOS, and explore possible mechanisms on how TCS may contribute to the development of clinical manifestations of PCOS., Design: Cross-sectional study., Setting: This study was conducted in one tertiary-level hospital located in Zhejiang, China., Participants: A total of 674 infertile women at 18-45 years of age were recruited in 2014-2015. Participants with (n=84) and without (n=212) PCOS with urinary TCS concentration available were included in the analyses., Methods: Urinary TCS concentration was measured using a high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry. Logistic regression model was used to examine the association between TCS and PCOS. Fractional polynomial regression models were built to fit the potential non-linear relationship between TCS concentrations and luteinising hormone (LH) and LH/follicle stimulate hormone (FSH)., Results: The PCOS group had significantly higher level of TCS concentration than the non-PCOS group (the median of TCS (IQR), μg/g creatinine: 1.49 (0.68-3.80) vs 1.06 (0.52-3.02), p=0.0407). Compared with the lowest tertile, the highest tertile of TCS concentration was associated with an increased odd of PCOS (OR 2.12, 95% CI 1.12 to 3.99). After adjusting for potential confounders, the significant association remained (OR 1.99, 95% CI 1.05 to 3.79). Positive relationships were found between TCS levels and LH and LH/FSH ratio in non-PCOS participants., Conclusions: TCS exposure at a relatively low level is associated with PCOS in Chinese women. Further epidemiological studies are needed to confirm our finding, which may have important public health implications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The effect of endometriosis on fecundity is unclear. Although surgery plays a vital role in the treatment of related infertility, pregnancy outcomes after laparoscopy are poorly correlated with the currently used staging system. To address this, the Endometriosis Fertility Index (EFI) was developed. This retrospective study was designed to assess the predictive value of the EFI for patients with endometriosis-associated infertility. A total of 1325 patients with endometriosis-associated infertility were eligible for inclusion, 1097 of whom were successfully interviewed and 228 lost to follow-up (17.21%). Cumulative pregnancy incidence (CPI) according to EFI scores were calculated by life table and by Kaplan-Meier survival curve analyses. The log-rank test was used to evaluate difference between the EFI groups. Receiver operating characteristic curves were plotted to obtain the optimal cut-off point for pregnancy prediction. A total of 505 (46.03%) patients conceived naturally. The difference in CPI among EFI scores 10, 7-9, 4-6, and 2-3 was statistically significant (P < 0.001) and increased with increasing EFI score. The optimal cut-off point was 7.5: sensitivity (68.51%); specificity (52.20%). This retrospective study indicates the value of the EFI score for predicting spontaneous pregnancy in women treated by laparoscopy for endometriosis-associated infertility., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To systematically review and appraise the existing evidence in relation to the efficacy and safety of pulsatile gonadotropin-releasing hormone (pGnRH) for the treatment of women with hypothalamic amenorrhea (HA)., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): A total of 35 studies (three randomized and 32 observational) encompassing 1,002 women with HA., Intervention(s): None., Main Outcome Measure(s): Primary outcomes: ovulation rate (OvR), pregnancy per ovulatory cycle rate (POR), and live birth per ovulatory cycle rate (LBOR)., Secondary Outcomes: multiple gestation (MG), ovarian hyperstimulation syndrome (OHSS), and superficial thrombophlebitis (ST) rates. The summary measures were expressed as proportions and 95% confidence intervals (CI)., Result(s): Pulsatile GnRH treatment appears to achieve high OvRs. A trend toward high PORs and LBORs among women with HA is demonstrated. SC pGnRH achieves comparable OvR compared with IV pGnRH. The incidence of OHSS is low and of mild severity. Treatment with pGnRH is associated with low but slightly higher MG rates compared with the general population. IV administered pGnRH is rarely associated with ST., Conclusion(s): The high OvRs leading to a high rate of singleton pregnancies and the low likelihood of OHSS render the pGnRH treatment modality both effective and safe for the treatment of women with HA of either primary or secondary origin., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether bisphenol A (BPA) exposure is associated with uterine decidualization and embryo implantation failure in mice., Design: Experimental animal study and in vitro study., Setting: University-based infertility center., Animal(s): ICR mice., Intervention(s): Mice treated with different doses of BPA; Ishikawa cells cultured in medium of different concentrations of BPA., Main Outcome Measure(s): Embryo implantation sites, uterine weight, quantitative real-time reverse transcriptase-polymerase chain reaction, Western blot analysis, hematoxylin and eosin staining, and immunohistochemical, cell proliferation, and statistical analyses., Result(s): In the experiment of mouse model, administration of 1-100 μg/kg/day of BPA by gavage led to reduction of the number of embryo implantation sites in a dose-dependent manner; 100 μg/kg/day of BPA statistically significantly reduced the number of implantation sites compared with the control group. The uterine weight change (the wet weight of the decidualized uterine horn divided by the wet weight of the undecidualized uterine horn of the mouse) in groups exposed to BPA (100-10,000 μg/kg/day) were statistically significantly lower compared with the control group. Immunohistochemical analysis demonstrated that administration of 100, 1,000, or 10,000 μg/kg/day of BPA by gavage statistically significantly down-regulated the expression of epithelial Na + channel α-subunit (ENaCα) in the luminal epithelial cells and desmin in decidual cells of the oil-induced decidualized uterine horns. Administration of 100 μg/kg/day BPA on embryo days 0.5-3.5 by gavage statistically significantly decreased the level of uterine serum and glucocorticoid-regulated kinase 1 (SGK1) protein expression on embryo days 4 and 6. After treatment with 0.001, 0.01, 0.1, or 1.0 μg/mL of BPA for 48 hours, the SGK1, ENaCα, and phospho-SGK1 protein expression of Ishikawa cells was down-regulated, and the effect of BPA on SGK1 could be abrogated by fulvestrant., Conclusion(s): Our study provides the first indication that BPA exposure at levels as low as 100 μg/kg/day can impair embryo implantation in mice and BPA can affect decidualization of the uterus in mouse model. Our results suggest that BPA can down-regulate SGK1 and ENaCα protein expression through estrogen receptors in Ishikawa cells., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare clinical outcomes of in vitro fertilization (IVF) cycles with the use of gestational carriers (GCs) with non-GC IVF cycles., Design: Retrospective cohort study of assisted reproductive technology (ART) cycles performed with (24,269) and without (1,313,452) the use of a GC., Setting: ART centers., Patient(s): Infertile patients seeking IVF with or without use of a GC., Interventions(s): Autologous and donor oocyte cycles, fresh and cryopreserved embryo transfer cycles., Main Outcome Measure(s): Live birth rate (LBR), twin and high-order multiple birth rates., Result(s): Approximately 2% of embryo transfers used a GC. Per embryo transfer, GCs had greater pregnancy rate and LBR across all IVF types compared with non-GC cycles in crude models and models adjusted a priori for potential confounders. For women with uterine-factor infertility, embryo transfer with the use of a GC resulted in a higher odds of live birth for autologous fresh embryos and for cryopreserved embryos compared with patients with non-uterine-factor infertility diagnoses., Conclusion(s): GC benefits LBRs for some patients seeking ART. The highest LBRs occurred when the indication for GC was uterine-factor infertility., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the current prevalence of and risk factors for infertility among couples of reproductive age in China., Design: Population-based cross-sectional study., Setting: We approached 25 270 couples in eight provinces/municipalities, of whom 18 571 (response rate 74%) were interviewed., Population: Couples living together and married for more than 1 year, of whom the female spouse was 20-49 years old., Methods: Women were approached via telephone and face-to-face conversation to complete the standardised and structured questionnaire by trained interviewers., Main Outcome Measures: Prevalence of and risk factors for infertility., Results: Among women 'at risk' of pregnancy, the prevalence of infertility was 15.5% (2680/17 275). Among 10 742 women attempting to become pregnant, the prevalence of infertility was 25.0% (2680/10 742), which increased with age in the second population. Among women who failed to achieve pregnancy in the last 12 months, 3470 finished our questionnaire about fertility care, and 55.2% (1915/3470) of them had sought medical help. Sociodemographic risk factors for infertility included lower educational level [adjusted odds ratio (aOR) 3.4, 95% CI 2.0-5.5] and employment (aOR 2.3, 95% CI 1.9-2.9). Clinical risk factors were irregular menstrual cycle (aOR 1.8, 95% CI 1.2-2.5), light menstrual blood volume (aOR 1.6, 95% CI 1.2-2.0), history of cervicitis (aOR 1.5, 95% CI 1.2-2.0) and endometriosis (aOR 3.1, 95% CI 1.1-9.3), previous stillbirth (aOR 2.1, 95% CI 1.3-3.3) and miscarriage (aOR 2.7, 95% CI 2.1-3.5). In addition, history of operation was a significant risk factor of infertility., Conclusions: Among couples of reproductive age in China, the prevalence of infertility was 25%, and almost half of the couples experiencing infertility had not sought medical help., Tweetable Abstract: In China, 25% of couples actively attempting to become pregnant suffered infertility., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Background: Elective frozen-embryo transfer has been shown to result in a higher live-birth rate than fresh-embryo transfer among anovulatory women with the polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer increases live-birth rates among ovulatory women with infertility., Methods: In this multicenter, randomized trial, we randomly assigned 2157 women who were undergoing their first in vitro fertilization cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up to two cleavage-stage embryos were transferred in each participant. The primary outcome was a live birth after the first embryo transfer., Results: The live-birth rate did not differ significantly between the frozen-embryo group and the fresh-embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between-group differences in the rates of implantation, clinical pregnancy, overall pregnancy loss, and ongoing pregnancy. Frozen-embryo transfer resulted in a significantly lower risk of the ovarian hyperstimulation syndrome than fresh-embryo transfer (0.6% vs. 2.0%; relative risk, 0.32; 95% CI, 0.14 to 0.74; P=0.005). The risks of obstetrical and neonatal complications and other adverse outcomes did not differ significantly between the two groups., Conclusions: The live-birth rate did not differ significantly between fresh-embryo transfer and frozen-embryo transfer among ovulatory women with infertility, but frozen-embryo transfer resulted in a lower risk of the ovarian hyperstimulation syndrome. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China; Chinese Clinical Trial Registry number, ChiCTR-IOR-14005406 .).

Purpose: Fatty acids have been shown to play an important role in oocyte competence and early implantation of the embryo. Our hypothesis-generating study sought to determine if individual fatty acids expressed as a percentage of total erythrocyte fatty acids are associated with embryo quality and other in vitro fertilization (IVF) outcomes., Methods: This was a prospective cohort study at an academic fertility center. Sixty women undergoing their first IVF cycle were recruited. Serum measurements of 22 fatty acids were obtained. We calculated each fatty acid as a percentage of total fatty acids, defined as the index for that individual fatty acid., Results: Omega-3 index had no correlation with IVF outcomes. A negative correlation was found between the trans fatty acid index, elaidic acid (EA), and IVF outcomes, including fertilization rate (r = - 0.261, p = 0.04), blastocyst conversion rate (r = - 0.41, p = 0.001), and number of usable blastocysts and embryos (r = - 0.411, p = 0.001). There was no correlation between EA index and number of oocytes retrieved, embryo grade, or clinical pregnancy. No consistent correlations were observed with the additional fatty acids analyzed., Conclusions: No correlation was observed between omega-3 index and IVF outcomes. Elevated erythrocyte EA index, the major trans fatty acid commonly consumed in hydrogenated oils, margarine, and fried foods, was negatively correlated with number of usable blastocysts and embryos, blastocyst conversion, and fertilization rate. Our findings suggest preliminary evidence that trans fat may be negatively associated with IVF outcomes.

Objective: To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW)., Design: Cross-sectional analysis nested in a retrospective observational study (n = 940)., Setting: Hospitals and associated private practices., Patient(s): Previously pregnant women (n = 268) within reproductive age in matched pairs., Intervention(s): Retrospective analysis of surgical reports and self-administered questionnaires., Main Outcome Measure(s): Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months' time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis)., Result(s): The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%-42.0%]) compared with CW (22.0% [16.7%-27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41-2.75). This remained significant in subfertile WwE (50.0% [40.7%-59.4%]) vs. CW (25.8% [8.5%-41.2%]) but not in fertile WwE (24.5% [16.3%-31.6%]) vs. CW (21.5% [15.9%-26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%-51.4%] vs. rASRM III/IV 30.8% [22.6%-38.7%], compared with 22.0% [16.7%-27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%-53.9%]) compared with ovarian endometriosis (28.6% [17.7%-38.7%]) and deep infiltrating endometriosis (33.9% [21.2%-46.0%]) compared with CW (22.0% [16.7%-27.0%])., Conclusion(s): Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage., Clinical Trial Registration Number: NCT02511626., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The longer term cardiovascular effects of fertility therapy are unknown., Objectives: The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes., Methods: We systematically searched published reports for studies addressing the question "does fertility therapy increase the risk of longer term cardiovascular outcomes?" We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not., Results: Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I 2  = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I 2  = 0%). Results were not pooled for hypertension (I 2  = 95.0%) and venous thromboembolism (I 2  = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I 2  = 0%)., Conclusions: The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed., Objective: The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility., Study Design: A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale., Results: Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility., Conclusion: Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This study aimed to explore valuable preconception predictors of gestational diabetes mellitus (GDM) in PCOS patients., Methods: A prospective cohort study enrolling infertile Chinese PCOS women treated with ovulation induction was performed. The endocrine, metabolic and physical features of all the patients were collected before pregnancy and then followed up to 6 weeks after delivery. The prevalence of GDM was determined during 24-28 gestational weeks. Logistic regression analysis and receiver operating characteristic (ROC) curves were applied to explore the risk factors and their predictive value for GDM., Results: A total of 94 infertile PCOS women who got singleton pregnancy by ovulation induction were enrolled in the study. Logistic regression analysis showed that the preconception insulin under the curve (IAUC) and sex hormone-binding globulin (SHBG) levels were two most significant risk factors for developing GDM (p = 0.014; p = 0.042, respectively). The area of SHBG and IAUC under the ROC curve were 0.806 (p < 0.001) and 0.775 (p = 0.001), respectively. The optimal cutoff values were failed to be calculated because of the limited group size., Conclusions: Low SHBG level and hyperinsulinism were both strongly associated with the development of GDM and might be two valuable predictors in PCOS patients.

Endometriosis is one of the main causes for female infertility. Previous studies suggested that perfluoroalkyl substances (PFASs), a group of ubiquitous environmental chemicals with properties of endocrine disruption and reproductive toxicity, were risk factors for endometriosis but there lacks direct evidence on the possible role of PFASs in endometriosis-related infertility. To fill this gap, we examined the association between PFASs and endometriosis-related infertility among Chinese reproductive-age women in a case-control study, which comprised 157 surgically confirmed endometriosis cases and 178 controls seeking infertility treatment because of male reproductive dysfunction in 2014 and 2015. Blood specimens were collected at the enrollment and analyzed for ten PFASs. Logistic regression was utilized to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for individual PFAS compound. Plasma concentrations of perfluorobutane sulfonic acid (PFBS) were associated with an increased risk of endometriosis-related infertility (second vs. lowest tertile: OR=3.74, 95% CI: 2.04, 6.84; highest vs. lowest tertile: OR=3.04, 95% CI: 1.65, 5.57). This association remained consistent when we restricted to subjects with no previous pregnancy (second vs. lowest tertile: OR=2.91, 95% CI: 1.28, 6.61; highest vs. lowest tertile: OR=3.41, 95% CI: 1.52, 7.65) or to subjects without other gynecologic pathology (second vs. lowest tertile: OR=4.65, 95% CI: 2.21, 9.82; highest vs. lowest tertile: OR=3.36, 95% CI: 1.58, 7.15). Plasma concentrations of perfluoroheptanoic acid (PFHpA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were inversely associated with endometriosis-related infertility, but the associations were attenuated in the sensitivity analyses. Our preliminary evidence suggests that exposure to PFBS may increase the risk of female infertility due to endometriosis. Future prospective studies are necessary to confirm these findings., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Hysterosalpingography (HSG) is the most frequently used diagnostic measure for simultaneously determining uterine abnormalities and tubal status among subfertile women. Despite several broader advantages such as availability and increased experience, the subjectivity involved during administration of the HSG procedure itself, and necessary imaging review, decreases the reliability and accuracy of HSG. In this study, we evaluated the time intervals between X-ray imaging during HSG procedure to establish the presence of distal tubal occlusion., Methods: Our study evaluated the HSG records of 89 women who underwent diagnostic laparoscopy for infertility work-up. Patients who were diagnosed with distal tubal occlusion upon receiving HSG and patients who demonstrated tubal patency on HSG were included in the study, to compare the time intervals in seconds from the tubal visualization view to the last fluoroscopic X-ray shot during the HSG procedure with tubal patency on diagnostic laparoscopy., Results: A statistically significant correlation regarding tubal patency between HSG procedures and diagnostic laparoscopy chromopertubation procedures was demonstrated. Although nearly statistically significant, the interval in seconds between the first HSG imaging and distal tubal filling was shorter for patients with patent tubes on diagnostic laparoscopy than patients with bilateral tubal occlusion (8.4±31.9 and 12.0±19.7, respectively; p=0.057). Time period intervals between the first and the last HSG, and between distal tubal filling to the last HSG of patients with patent tubes on diagnostic laparoscopy and patients with bilateral distal tubal occlusion were found to be statistically similar., Conclusion: Although a trend exists towards shorter time period intervals between the first uterine visualization and distal tubal filling graphy among patients with tubal patency, rather than patients with distal tubal occlusion confirmed by diagnostic laparoscopy, clinically reliable objective time period intervals for finalizing the HSG procedure and proceeding with diagnostic laparoscopy due to distal tubal occlusion diagnosis on HSG could not be detected., (Copyright © 2016. Published by Elsevier Taiwan LLC.)