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Embryo migration is defined as the movement of embryos to implant at the exact site in the endometrial cavity during assisted reproductive technology (ART). We aimed to evaluate the impact of embryo migration on clinical pregnancy (CPR) and live birth rates (LBR) in fresh oocyte donation (OD) cycles. A total of 611 fresh OD cycles was recruited in this prospective cohort study. All embryos were expulsed to upper-middle uterus between 10 and 20 mm from the fundus. Air bubble-fundus distance was measured using ultrasound (USG) at the time of embryo transfer (ET) and then 60 minutes after ET. Patients were divided into 3 groups; first group consisted of patients whose embryos migrated towards fundus, second group whose embryos remained between 10 and 20 mm from fundus and the third group including embryos which migrated towards cervix. There was no significant difference between the groups regarding CPR and LBR ( p  = 0.359 and p  = 0.865, respectively). Our study revealed that embryo migration was a fact and almost 22% of embryos migrated towards the fundus or the cervix. On the other hand, whether the embryo stayed static or migrated, CPR and LBR did not differ significantly in fresh OD cycles.

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.)

Objective: With remarkable deficiency in both oocyte stock and competence, the prognosis of IVF-ET in diminished ovarian reserve (DOR) is obstinately poor, underscoring warranted optimization to current procedures. We compared the efficacy of dual-trigger (hCG plus GnRH-a) and hCG alone on the outcomes for DOR patients., Study Design: A total of 381 couples and 857 controlled ovarian stimulation (COS) cycles, and 222 couples and 366 frozen embryo transfer (FET) ones were included. The intermediate outcomes during oocyte retrieval and in vitro culture were compared based on COS dataset, while outcomes after embryo transfer analyzed based on FET dataset. The marginal effect of all study factors and covariates were evaluated with a cluster-weighted GEE model., Results and Conclusion: Neither the intermediate nor implantation outcomes were improved by dual-trigger. The OR values were 1.08 (95 % CI: 0.41-2.78) for retrieval cancellation, 1.33 (95 % CI: 0.89-2.00) for oocyte harvest, 1.04(95 %CI: 0.94-1.15) for viable embryo and 1.03(95 %CI: 0.88-1.19) for top-quality embryo. Similarly, the ORs were 0.90 (95 %CI: 0.62-1.30) for implantation and 0.97 (95 %CI: 0.56-1.69) for clinical pregnancy. This equivalence remained unchanged after adjusting for the covariates such as age, BMI, controlled ovarian stimulation protocols, etc. Thus, dual-trigger cannot provide significant advantage over hCG in related to immediate or clinical outcomes of IVF-ET treatments in DOR patients., Competing Interests: Declaration of competing interest 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Research Question: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring?, Design: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors., Results: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544)., Conclusion: This study suggests that children born through FET have increased risk of developing food allergy in early childhood., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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).)

Background: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms., Methods: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET)., Results: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups., Conclusion: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation., (© 2024. The Author(s).)

Purpose: To evaluate the efficacy of magnetic-activated cell sorting (MACS) or testicular sperm aspiration (TESA) to improve reproductive outcomes in cases with elevated sperm DNA fragmentation undergoing assisted reproduction., Methods: This randomized controlled trial included couples with failed IVF cycles and sperm DNA fragmentation > 30%. Sperm DNA fragmentation was assessed using the sperm chromatin structure assay (SCSA) method. Participants were randomly assigned to either the MACS or TESA group. Testicular sperm retrieval was performed for the TESA group, while MACS involved sperm selection using magnetic beads. Extended blastocyst culture, freeze all policy of blastocysts by vitrification, and frozen embryo transfer were undertaken as per clinic's standard operating protocols. Blastocyst formation rate, implantation rate, miscarriage rate, multiple pregnancy rate, and live birth rate were analyzed and compared between MACS and TESA groups., Results: There were no significant differences in female age, male age, or sperm DNA fragmentation index (DFI) between the MACS and TESA groups. The blastocyst conversion rate was slightly higher in the TESA group (39%) compared to the MACS group (32%). However, the MACS group had a higher implantation rate (50%) than the TESA group (35%). Miscarriage rates, multiple pregnancy rates, and live birth rates did not show statistically significant differences between the groups. A chi-squared test was conducted to compare categorical variables, and t-tests were done to compare continuous variables., Conclusion: In cases with raised sperm DNA fragmentation, sperm selection by MACS or TESA seems to offer comparable reproductive outcomes. There seems no superiority of one intervention over the other in cases with raised sperm DNA fragmentation undergoing assisted reproduction. Both interventions seem to be beneficial for couples seeking assisted reproduction with raised sperm DNA fragmentation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies (ACA) receiving in vitro fertilization (IVF)-embryo transfer (ET) and natural conception., Methods: A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure., Results: The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P <0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P <0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the two pronucleus (2PN) rate did not increase compared to c-IVF cycles ( P >0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P <0.05). After 1-2 months of immuno-suppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P >0.05), but there was an improvement in the 2PN embryo cleavage rate ( P <0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P <0.05), with no significant differences in the miscarriage rate between the two groups ( P >0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy., Conclusions: Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

Objective: To compare the treatment effects of laparoscopy versus laparotomy on heterotopic pregnancy (HP) after in vitro fertilization-embryo transfer (IVF-ET)., Methods: The retrospective case-control study enrolled 109 patients diagnosed with HP after IVF-ET treatment in our hospital from January 2009 to March 2020. All patients received surgical treatment by either laparoscopy or laparotomy. Data for general characteristics, diagnostic features, surgical parameters, as well as perinatal and neonatal outcomes were collected., Results: Sixty-two patients received laparoscopy and 47 received laparotomy. Significantly lower percentage of large hemoperitoneum (P = 0.001), shorter surgery duration (P < 0.001), less intraoperative blood loss (P = 0.001), higher rates of general anesthesia (P < 0.001), and lower cesarean section rates for singletons (P = 0.003) were found in the laparoscopy group. The perinatal and neonatal outcomes were comparable between the two groups. When interstitial pregnancy was considered alone, the surgical blood loss was significantly reduced in the laparoscopy group (P = 0.021), but there was no significant difference in hemoperitoneum, surgery duration, or perinatal and neonatal outcomes in singletons., Conclusion: Both laparoscopy and laparotomy are effective surgical treatments for HP after IVF-ET. Laparoscopy is minimally invasive but laparotomy can be an alternative in emergency situations., (© 2023 International Federation of Gynecology and Obstetrics.)

This study aimed to evaluate the effect of the cryopreservation duration (up to 160 months) on the clinical and neonatal outcomes of slow-frozen early-cleavage human embryos. Clinical data collected between February 2013 and August 2017 were included in this retrospective study. Cases were classified into five groups by the duration of cryopreservation: Group 1, 6-12 months; Group 2, 13-36 months; Group 3, 37-60 months; Group 4, 61-84 months; and Group 5, >84 months. The embryo survival rate, implantation rate, clinical pregnancy rate, live-birth rate, newborn sex ratio, singleton gestational age, singleton birth weight and malformation rate were compared between the groups. The cryopreservation duration did not significantly affect the rates of clinical pregnancy ( P = 0.119) and live birth ( P = 0.354), the newborn sex ratio ( P = 0.614) or the singleton gestational age ( P = 0.212) and birthweight ( P = 0.212). Although decreases in the embryo survival and implantation rates were observed in groups 4 and 5 compared with those in groups 1-3, these differences were not statistically significant ( P = 0.329, P = 0.279, respectively). Long-term cryopreservation does not appear to adversely affect the clinical and neonatal outcomes of slow-frozen early-cleavage human embryos.

Objective: To investigate the relationship between the embryo frozen time and live birth rate (LBR) in women having a freeze-all cycle., Design: Retrospective cohort study., Setting: Academic hospital., Patient(s): Women who underwent their first vitrified-warmed cycles from January 2013 to December 2019., Intervention(s): Embryo storage time., Main Outcome Measure(s): The primary outcome was the LBR., Result(s): A total of 14,928 women were eligible for the analysis. Women with the frozen time of transferred embryos for 2-5 months were associated with a higher LBR compared with other groups. The results were confirmed by an inverted U curve in the restricted cubic splines before as well as after adjustment for covariables, which suggested that an embryo storage time of 3-4 months was associated with the highest LBR. Subgroup analyses demonstrated that the inverted U curve relationship between embryo storage time and LBR was only observed in women with the high response. Sensitivity analyses in women with at least one good-quality embryo for transfer, in women aged <36 years at embryo transfer, or in women with double cleavage embryo transfer showed that the association remained valid. The association was weakened in women with single blastocyst transfer probably because of the small sample size in these women., Conclusion(s): An inverted U-shaped relationship was found between embryo storage time and treatment success in women with high ovarian response in freeze-all embryo transfer cycles. Prolonged storage time of >6 months was associated with reduced pregnancy rates., (Copyright © 2022. Published by Elsevier Inc.)

A randomized sibling-embryo pilot trial investigated whether two ways of laser-assisted hatching result in different blastulation and clinical outcomes after extended in vitro culture process of highly fragmented day-3 cleavage embryos. From 92 couples, a total of 315 highly fragmented day-3 embryos (the fragmentation >25%) were recruited and randomized into laser-assisted zona thinning (LAT, n=157) and opening (LAO, n=158) groups, and then underwent a blastocyst culture in vitro . The main endpoint measurements including blastocyst formation and grading as well as the clinical pregnancy after blastocyst transfer were obtained during the treatment procedure of in vitro fertilization and embryo transfer, and then analyzed with generalized estimating equation (GEE) and/or time-to blastocyst analysis models. A total of 166 day-3 embryos developed into blastocyst stage (52.70%), of which 97 were viable blastocysts (30.79%), and 42 top-quality ones (13.33%). LAT did not have any inferior or superior to LAO in the endpoints of either total, viable, top-quality or hatched blastocyst formation, with the ORs (95%CI) from GEE model as 0.89 (0.55-1.45), 0.71 (0.42-1.21), 1.12 (0.56-2.25) and 0.68 (0.42-1.12) respectively for LAT treatment. And the time-to-blastocyst analysis showed a similar result. Additionally, no difference in clinical outcomes after blastocyst transfer was found between the two groups. The author concluded that when applying the LAHs during the extended culture of highly fragmented embryos, both LAT and LAO can generate a promising clinical outcome, and the LAT operation be equivalent to the LAO. Future well-designed, multiple-center, larger-sample investigations are required to ascertain above conclusion., 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 © 2022 Zhang, Zhou, Wu, Wu, Li, Zhang, Jin, Shu, Xu and Shu.)

Background: Biochemical pregnancy is a type of embryo transfer failure, patients with unexplained repeated implantation failure (RIF) also have higher biochemical pregnancy rate. Our study intends to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) in patients with unexplained RIF with low hCG levels in early pregnancy., Methods: Unexplained RIF patients with low hCG levels after embryo transfer were allocated. G-CSF were administrated from the ninth days after embryo transfer. Clinical pregnancy, miscarriage and live birth rates were evaluated., Results: The clinical pregnancy and live birth rates were 52.5% and 30%., Conclusion: G-CSF is an effective treatment for potential biochemical pregnancy in unexplained RIF patients.

Background: Parental body mass index (BMI) is associated with pregnancy outcomes. But the effect of parental prepregnancy BMI on offspring conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially the birth defect, remains to be determined. This study aimed to investigate the associations of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles., Methods: We conducted a retrospective cohort study including 5741 couples in their first fresh IVF/ICSI cycles admitted to Women's Hospital, School of Medicine, Zhejiang University from January 2013 to July 2016. The primary outcome was birth defects, which was classified according to the International Classification of Diseases, 10th Revision. Secondary outcomes included preterm delivery rate, infant gender, birth weight, small-for-gestational age (SGA) and large-for-gestational age (LGA). Multilevel regression analyses were used to assess the associations of parental prepregnancy BMI with neonatal outcomes and birth defect., Results: In singletons, couples with prepregnancy BMI ≥25 kg/m 2 had higher odds of LGA than those with BMI < 25 kg/m 2 . The birth defect rate was significantly higher when paternal prepregnancy BMI ≥25 kg/m 2 in IVF cycles (aOR 1.82, 95% CI 1.06-3.10) and maternal BMI ≥25 kg/m 2 in ICSI cycles (aOR 4.89, 95% CI 1.45-16.53). For subcategories of birth defects, only the odds of congenital malformations of musculoskeletal system was significantly increased in IVF offspring with paternal BMI ≥25 kg/m 2 (aOR 4.55, 95% CI 1.32-15.71). For twins, there was no significant difference among four groups, except for the lower birth weight of IVF female infants., Conclusions: Parental prepregnancy BMI ≥25 kg/m 2 is associated with higher incidence of LGA in IVF/ICSI singletons. Paternal prepregnancy BMI ≥25 kg/m 2 was likely to have higher risk of birth defect in IVF offspring than those with BMI < 25 kg/m 2 , particularly in the musculoskeletal system. It is essential for overweight or obesity couples to lose weight before IVF/ICSI treatments., (© 2021. The Author(s).)

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.)

Background: There has been increasing interest in the relationship between body mass index(BMI) and pregnancy outcomes, especially in women undergoing frozen embryo transfer(FET). Several observational studies have been published, but so far with conflicting results., Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Pubmed, Embase, Cochrane Library, Clinicaltrails.gov and Web of Science databases were searched based on established search strategy from inception through January 2021., Results: Twelve studies were eligible. In women following FET, high BMI (BMI ≥ 23 kg/m 2 ) was associated with an impaired live birth rate (LBR, OR: 0.89, 95% CI: 0.82-0.96, P = 0.002), but wasn't associated with the implantation rate or the clinical pregnancy rate. Subgroup analysis revealed higher LBR for women didn't complicated by polycystic ovary syndrome (PCOS, OR: 0.96, 95% CI: 0.85-1.08, P = 0.46) and women with blastocyst transferred (OR: 0.89, 95% CI: 0.68-1.16, P = 0.40). LBR did not differ between the low BMI group (BMI < 18.5 kg/m 2 ) and the normal weight group., Conclusions: Our study showed that high BMI in women is negatively associated with LBR in FET cycles, whereas low BMI isn't. The results of subgroup analysis implied a need for women with a high BMI to get individualized weight management and treatment. Further evidence is still required to optimize preconception health and develop Nutritional and exercise guidelines., (© 2021. The Author(s).)

Background: Laser-assisted hatching (LAH) has been widely applied to facilitate blastocyst hatching in IVF-ET treatment, however, the effect of LAH on subsequent development and clinical outcomes of the lower grade cleavage stage embryos (LGCE) remains unknown. Our study aimed at evaluating the effect of LAH on blastocyst formation and the clinical pregnancy outcomes of LGCE embryos after transfer., Methods: A total of 608 cycles of IVF/ICSI treatment from November 2017 to September 2019 were included in our study as follows: 296 in the LAH group and 312 in the N-LAH group. The total blastocyst rate, usable blastocyst rate, good-grade blastocyst rate and clinical pregnancy rate were statistically compared between the two groups., Results: The total blastocyst rate (50.7% vs 40.2%, P < 0.001), usable blastocyst rate (31.0% vs 18.6%, P < 0.001) were significantly higher in the LAH group than those in the N-LAH group. After analysis of generalized estimating equations, LAH was positively correlated with the blastocyst rate (B = 0.201, OR 95% CI = 1.074-1.393, P = 0.002), usable blastocyst rate (B = 0.478, OR 95% CI = 1.331-1.955, P < 0.001). However, the clinical pregnancy rate after blastocyst transfer did not differ between LAH group and N-LAH group (49.4% vs 40.0%, P > 0.05, respectively)., Conclusions: A higher proportion of total blastocysts and usable blastocysts can be obtained by LAH in LGCE, which may be beneficial to the outcome of the IVF/ICSI-ET cycle., (© 2021. The Author(s).)

This study evaluated pregnancy results after fresh and frozen embryo transfer in males with infertility due to non-obstructive azoospermia and oligoasthenoteratozoospermia. In this retrospective study, a total of 801 embryo transfer cycles were followed up, including 423 fresh embryo transfers and 378 frozen embryo transfers in which intracytoplasmic sperm injection (ICSI) was performed because of male infertility. This study included females aged 28-38 years without uterine, endometrial, ovarian and tubal abnormalities and with regular menstrual cycles (n=801), and males aged 28-38 years with non-obstructive azoospermia and oligoasthenoteratozoospermia. Descriptive statistical methods and the independent t-test were used in the comparison of two groups with normal distribution, the Mann-Whitney U test was used in the comparison of two groups without normal distribution, and the Chi-square test was used to compare categorical variables. There were no statistically significant differences between the fresh embryo transfer group and frozen embryo transfer group in terms of rates of pregnancy, biochemical pregnancy, clinical pregnancy, live birth rate, and abortion rate. There was no difference between fresh embryo transfer and frozen embryo transfer in terms of pregnancy results in couples with non-obstructive azoospermia and oligoasthenoteratozoospermia as male infertility factor.

Background: Is freeze-all strategy effective in terms of cumulative live birth rates (CLBRs) in all patients?, Methods: This retrospective single-center study analyzed the CLBRs of 2523 patients undergoing fresh or electively frozen blastocyst transfer cycles. In 1047, cycles, the fresh embryo transfer (ET) strategy was applied for the 1st ET, whereas electively frozen ET (e-FET) was performed in 1476 cycles. Female age ≤ 37 and blastocysts frozen via vitrification were included. The patients in each arm were further stratified into four subgroups according to the number of oocytes retrieved as follows: Group A: 1-5, group B: 6-10, group C: 11-15 and group D: 16-25 oocytes retrieved. The primary endpoint was the CLBR. The secondary endpoints were the ovarian hyperstimulation syndrome (OHSS) rate and the live birth rates (LBRs) following fresh ETs and e-FETs for the first transfers., Result(s): The CLBR was similar between the fresh ET and e-FET arms in group A (35/76 (46.1%) vs 29/67 (43.3%), p = 0.74) and group B (165/275 (60%) vs 216/324 (66.7%), p = 0.091), whereas significantly higher rates were detected in favor of the e-FET arm within group C (328/460 (71.3%) vs 201/348 (57.8%), p<0.001) and group D (227/348 (65.2%), vs 446/625 (71.5%), p<0.001). The OHSS rate was also found to be higher in the fresh ET arm among group C (12/348 (3.4%) vs 0/460 (0%), p<0.001) and group D (38/348 (10.9%) vs 3/625 (0.5%), p<0.001) patients than e-FET arm. Perinatal and obstetrical outcomes were nonsignificantly different between fresh and e-FET arms. However, the birth weights were significantly lower for fresh ET, 3064 versus 3201 g for singletons (p<0.001)., Conclusion: Compared with a fresh-transfer strategy, the e-FET strategy resulted in a higher CLBR among patients with >10 oocytes retrieved during stimulated cycles., Competing Interests: Authors FKB, NET, MG, SE, NF and MB are employees of Bahceci Health Group. ZY is an employee of Cyprus Science University. There are no patents, products in development, or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: This study investigated the medical coping styles of female patients treated with in vitro fertilization and embryonic transfer (IVF-ET), and analyzed the effects of alexithymia and social support on their choice of coping style., Methods: A survey was conducted with 285 female patients undergoing IVF-ET in a reproductive medical center of a third-grade class-A hospital in China using the Medical Coping Modes Questionnaire, the Social Support Rating Scale, and the Toronto Alexithymia scale., Results: Patients who underwent IVF-ET treatment had a higher score for avoidance as a coping mode than did normal controls. Utilization of social support predicted the use of confrontation as a coping style. Difficulty identifying feelings, objective support, and utilization of social support were factors in the choice of avoidance as a coping style, and length of infertility treatment, difficulty identifying feelings, and subjective support predicted patients' use of the acceptance-resignation as a coping style., Conclusion: Patients who undergo IVF-ET generally select the coping style of avoidance, which is not conducive to treatment. Targeted intervention strategies should be developed based on the factors influencing patients' choice of coping style(s) to guide them in choosing positive coping methods, improve compliance, and achieve successful pregnancy outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objective: To compare the clinical pregnancy and live birth results of fresh embryo transfer (ET) and selective frozen embryo transfer (sFET) in cohort of infertile patients aged between 18-42 years of age in single IVF center., Materials and Methods: In this retrospective cross-sectional study, the clinical and live birth results of 620 fresh embryo transfer cycles and 580 frozen embryo transfer cycles were investigated in Sisli Kolan International Hospital Fertility Unit between 2015-2018., Results: Age, BMI, causes of infertility, duration of infertility, ovulation induction protocols, the number of oocytes collected and the thickness of endometrium on the day of transfer were similar in the ET and sFET groups. More good quality embryos were obtained in sFET group. The clinical pregnancy and live birth rates were 71.04 % and 59.31 % in the sFET groups, and 56.77 % and 44.52 % in the ET group, respectively (p < 0.05)., Conclusion: Pregnancy, clinical pregnancy and live birth rates were higher in frozen embryo transfer cycles than in fresh embryo cycles. However, appropriate in vitro fertilization and embryo transfer methods suitable for each patient should be determined before choosing fresh ET or sFET treatment modalities., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper. No conflict of interest was declared by the authors., (Copyright © 2020 Elsevier Masson SAS. 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.)

In vitro fertilization and embryo transplantation (IVF-ET) technology is one of the main treatments for infertility. But IVF-ET is expensive and has not be covered by health insurance in most developing countries. Therefore, how to obtain the maximum success rate with the minimum cost is a common concern of clinicians and patients. At present, the economic studies on IVF-ET mainly focus on different ovulation stimulating drugs, different ovulation stimulating protocols, different transplantation methods and the number of transplants. But the process of IVF-ET is complex, the relevant methods of economic study are diverse, and there are no unified standard for outcome indicators, so there is no unified conclusion for more economical and effective protocol by now. Therefore, to analyze the economic studies of IVF-ET, and to explore appropriate evaluation methods and cost-effective protocols will be helpful for reasonable allocation of medical resources and guidance of clinical selection. It would provide policy reference to include the costs of IVF-ET treatment in health insurance in the future.

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.

Purpose: The occurrence of diminished ovarian reserve (DOR) in women was growing in recent years. Although in vitro fertilization and embryo transfer (IVF-ET) became an effective treatment for DOR, the live-birth (LB) rate remains unsatisfactory. This study aimed to investigate the impact factors of LB rate in women with DOR undergoing assisted reproduction., Methods: This was a single-center retrospective cohort study. A total of 2277 IVF-ET or ICSI cycles from 1957 DOR women were analysed. Impact factors of LB rate were explored via Student's t test, Pearson's Chi-square test, and multivariate logistic regression models., Results: There were statistically significant differences in maternal age (P < 0.001), duration of infertility (P < 0.001), female body mass index (P = 0.039), first IVF cycle (P = 0.004), poor ovarian response (P < 0.001), paternal age (P < 0.001), total gonadotropin dose (P = 0.010), endometrial thickness (P = 0.021), number of follicles ≥ 14 mm (P = 0.007), number of oocytes retrieved (P < 0.001), number of frozen embryos (P = 0.014), and the stage (P < 0.001) and number (P < 0.001) of embryos transferred between the non-live-birth (NLB) and LB groups. However, only factors of maternal age, the stage and number of embryos transferred remained different after adjusting for potential confounders., Conclusions: Maternal age, the stage and number of embryos transferred were independent impact factors affecting the live-birth rate in women with DOR seeking for assisted conception.

Background: Despite limited information on neonatal safety, the transfer of frozen-thawed cleavage-stage embryos with blastomere loss is common in women undergoing in vitro fertilization. We aimed to evaluate the pregnancy outcomes and safety of frozen-thawed cleavage-stage embryos with blastomere loss., Methods: This prospective, multicenter, cohort study included all frozen-thawed cleavage-stage embryo transfer (FET) cycles between 2002 and 2012. Pregnancy outcomes and subsequent neonatal outcomes were compared between FET cycles with intact embryos and those with blastomere loss., Results: A total of 12,105 FET cycles were included in the analysis (2259 cycles in the blastomere loss group and 9846 cycles in the intact embryo group). The blastomere loss group showed significantly poorer outcomes with respect to implantation, pregnancy, and live birth rates than the intact embryo group. However, following embryo implantation, the two groups were similar with respect to live birth rates per clinical pregnancy. Among multiple pregnancies (4229 neonates), neonates from the blastomere loss group were at an increased risk of being small for gestational age (aOR = 1.50, 95% CI 1.00-2.25) compared to those from the intact group. A similar trend was observed among singletons (aOR = 1.84, 95% CI 0.99-3.37). No associations were found between blastomere loss and the subsequent occurrence of congenital anomalies or neonatal mortality. However, neonates from the blastomere loss group were at an increased risk of transient tachypnea of the newborn (aOR = 5.21, 95% CI 2.42-11.22)., Conclusions: The transfer of embryos with blastomere loss is associated with reduced conception rates. Once the damaged embryos have implanted, pregnancies appear to have the same probability of progressing to live birth but with an increased risk of small for gestational age neonates and transient tachypnea of the newborn., Study Registration: This study was retrospectively registered at Chinese Clinical Trial Registry. Registration number: ChiCTR-OOC-16007753 . Registration date: 13 January 2016.

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.)

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 .).

Although controversial, increasing paternal age has been shown to negatively affect assisted reproductive technology (ART) outcomes and success rates. Most studies investigating the effect of paternal age on ART outcomes use a donor oocyte model to minimize maternal aneuploidy contribution. This study sought to determine whether increasing paternal age is associated with adverse in vitro fertilization (IVF) outcomes when aneuploidy is minimized using preimplantation genetic screening. There were 573 single thawed euploid embryo transfers from 473 patients undergoing oocyte donor and autologous IVF cycles. Cycles were categorized according to paternal age at oocyte retrieval, and an age adjustment was performed for maternal age in order to evaluate for an isolated paternal age effect. Fertilization rate was found to decrease significantly with increasing paternal age ( P = .04). After controlling for oocyte age, there was no significant difference in pregnancy outcomes across all paternal age categories after euploid embryo transfer, including implantation rate ( P = .23), clinical pregnancy rate ( P = .51), and spontaneous abortion rate ( P = .55). Therefore, if a couple is able to produce and transfer a single thawed euploid embryo, no difference in IVF pregnancy outcomes is identified with increasing paternal age.

Objective: The aims of this study were to summarize the clinical features of patients with heterotopic pregnancy (HP) following embryo transfer (ET) and explore the risk factors for miscarriage after surgery., Methods: All patients with HP following ET treated by surgery between August 2014 and August 2015 in Chongqing Health Center for Women and Children were retrospectively reviewed., Results: Fifty-five patients were identified, including 40 with tubal HP, 9 interstitial HP and 6 cornual HP. The most frequent manifestations before diagnosis was abdominal pain (29.1%), while 19 patients (34.5%) had no symptoms before diagnosis. The sensitivity of symptoms for HP was 65.5%. Gestational age at symptom onset of these patients with symptoms (n = 36) was 5.8 weeks (range 4.7-8.1). Forty-seven patients (85.5%) were suspected of HP when they received first transvaginal ultrasonography (TVS). The mean gestational age at diagnosis was 6.3 weeks (range 4.7-8.3, 16-41 days after ET). First TVS suggesting HP (P = 0.000) and first TVS performed before day 27 (P = 0.000) were two independent predictors for gestational age at diagnosis. Gestational age at surgery day was 6.7 weeks (range 5.3-10.7). Fifty-one patients (92.7%) resulted in a live birth. Gestational age at surgery day was the only independent risk factor for miscarriage in patients with HP treated by laparotomy (OR 0.003, 95% CI 0.001-0.604)., Conclusions: Routine TVS at day 27 after ET could facilitate the diagnosis of HP, symptoms onset before or after day 27 are clues to early diagnosis. Prompt surgery after diagnosis may improve the prognosis of HP following ET.

Objective: To investigate the effect of low and high oxygen concentration on embryo development, pregnancy outcome and birth defects of in vitro fertilization-embryo transfer (IVF-ET)., Methods: According to the oxygen concentration of in vitro culture environment, the IVF-ET performed in the Women's Hospital, Zhejiang University School of Medicine during 2013 and 2015 were divided into low oxygen concentration group ( n =2036, 5% O 2 ) and high oxygen concentration group ( n =4617, 20% O 2 ). The rate of fertilization, good quality embryo, clinical pregnancy, ectopic pregnancy, abortion and birth defect were compared between two groups., Results: The good quality embryo rate was significantly higher in the low oxygen concentration group ( P <0.05). However, no significant differences were found between two groups in the rate of fertilization, clinical pregnancy, ectopic pregnancy, abortion and birth defect (all P >0.05)., Conclusions: Low oxygen environment may improve the potential of embryonic development, but its impact on pregnancy outcome and birth defect is not significant.

Objective: To investigate the effects of embryo cryopreservation and thawing on clinical outcomes of transplantable embryos after preimplantation genetic diagnosis (PGD) or preimplantation genetic screening (PGS) in cleavage-stage., Methods: The clinical data of 302 cases (including 118 cases using frozen/thawing embryos and 184 cases using fresh embryos) undergoing PGD/PGS in Women's Hospital, Zhejiang University School of Medicine during January 2011 and December 2016 were retrospectively analyzed. The pregnancy rate, implantation rate, live birth rate and abortion rate of fresh and frozen-thawed embryo transfer (FET) cycles were compared. And the influencing factors for pregnancy outcome was analyzed by multivariate logistic regression., Results: The rate of normal or balanced translocation embryos in fresh cycle was higher than that in FET cycle (23.52% vs 16.67%, P <0.05), and the average number of transplanted embryos was more than that in FET cycle (1.54±0.56 vs 1.33±0.51, P <0.05). But there were no significant differences in pregnancy rate (36.42% vs 40.00%, P >0.05), implantation rate (26.62% vs 32.91%, P >0.05), abortion rate (19.44% vs 8.33%, P >0.05) and live birth rate (25.96% vs 28.33%, P >0.05) between fresh cycle and FET cycle. Multivariate logistic regression showed that, parent ages, embryo status (fresh or frozen), the mode of PGD/PGS and the findings of PGD/PGS had no impact on pregnancy outcome (all P >0.05)., Conclusions: Cryopreservation do not have significant effects on the clinical outcomes of transplantable embryos after PGD/PGS in cleavage-stage.

Purpose: Couples as dyads suffer from the diagnosis of infertility and related treatment. These couples commonly experience emotional and physical pain and tension in their marital lives. The purpose of this study is to report on the process of developing a potentially feasible and effective complex intervention for couples undergoing in vitro fertilization treatment in China., Methods: The Medical Research Council (MRC) framework for developing and evaluating the complex intervention was adopted to guide the development of the Partnership and Coping Enhancement Programme (PCEP). In developing the PCEP, three steps were taken, namely, (1) identifying evidence by conducting literature reviews, a concept analysis and a qualitative study; (2) identifying/developing a theory-in this case, a preliminary Endurance with Partnership Conceptual Framework (P-EPCF) was proposed; and (3) modelling the process and outcomes of the PCEP., Results: The PCEP that was developed is targeted mainly at the domains of the partnership mediators of stress in the P-EPCF. It consists of two sections-partnership and coping-and will be delivered to infertile couples on the day of embryo transfer. The main focuses of the programme are to facilitate mutual sharing and support in infertile couples, and to improve their individual and dyadic coping strategies while undergoing IVF treatment, especially in the period when they are waiting for the results of a pregnancy test and after the disclosure of a negative treatment outcome. The programme is couple-based, consisting of experience sharing, psychoeducation, meditation exercise, skill practise and supplemental written materials., Conclusions: The Partnership and Coping Enhancement Programme (PCEP) for couples undergoing in vitro fertilization treatment was developed according to the guideline of the MRC framework. It is recommended that a pilot study be conducted to evaluate its feasibility and to model the process and outcomes of the programme.

Purpose: The aim was to investigate if improved survival rates could be achieved using a new formulation of solutions for slow freezing of human cleavage stage embryos., Methods: The evaluation was divided into two parts. The first part was a retrospective analysis of results obtained after freezing and thawing of day 3 embryos from 400 women using an old formulation of cryopreservation solutions compared to results from 108 women for which cryopreservation had been performed using new compositions of solutions. The second part was prospective, adding cycles until similar numbers of patients had been included in both groups. In total, 2274 embryos from 897 patients were thawed using the old formulation of solutions while 1273 embryos from 542 patients were frozen and thawed using the new solutions. The primary endpoint was survival rate., Results: With the new solutions, the survival rate increased from 82.1 to 94.4 % and the complete embryo survival rate increased from 54.9 to 81.3 %. The implantation rate, clinical pregnancy rate per embryo transfer, and per cycle were 28.2, 45.2, and 43.7 %, respectively, using the old formulations of cryosolutions. With the new solutions, the results reached 33.7, 54.1, and 54.1 %, respectively. All differences in results were statistically significant. The number of cancelled embryo transfers due to no survived embryos was 18 with the old solutions and 0 using the new solutions., Conclusion: With the new composition of solutions for slow freezing and thawing of embryos, significantly improved results were obtained. Additionally, the number of cancelled embryo transfers was reduced., Competing Interests: Compliance with ethical standards All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Conflicts of interest The authors declare that they have no conflicts of interest. Funding This study was funded by China Natural Science Fundation (Grant No.81370761) and China National Key Technology Support Program (Grant No. N20120266-04).

Objective: To determine if the addition of continuous morphokinetic data improves reproductive outcomes when all embryos are cultured in a closed system., Design: Prospective, randomized, controlled study., Setting: Single academic center., Patient(s): A total of 235 patients undergoing fresh autologous IVF cycles with at least four embryos, cultured in the Embryoscope: 116 patients randomized to conventional once-daily morphologic embryo screening (CS) and 119 to additional time-lapse kinetic monitoring (TLM) for selection., Intervention(s): TLM versus CS., Main Outcome Measure(s): Intrauterine clinical pregnancy (CPR) and implantation (IR) rates., Result(s): CPR and IR were similar overall (TLM vs. CS, respectively: CPR 68% vs. 63%; IR 51% vs. 45%) and with blastocyst transfers (CPR 74% vs. 67%; IR 56% vs. 51%). CPR with day 5 transfer was threefold higher than day 3 transfer, but group (TLM vs. CS) was not a significant predictor of clinical pregnancy or implantation. Significantly more multinucleation was detected when CS embryos were retrospectively reviewed with the use of TLM (7.0% vs. 35.3%), and multinucleation was independently associated with decreased rates of implantation. Time to the start of blastulation of <100 hours after insemination and the morphokinetic scoring system used in the TLM group were independently associated with implantation., Conclusion(s): The addition of time-lapse morphokinetic data did not significantly improve clinical reproductive outcomes in all patients and in those with blastocyst transfers. Absence of multinucleation, timing of blastulation, and morphokinetic score were found to be associated with blastocyst implantation rates., Clinical Trial Registration Number: NCT02081859., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with secondary infertility., Methods: The clinical, laboratory and follow-up data of 1129 cycles in 1099 patients with secondary infertility undergoing IVF-ET in Women's Hospital, Zhejiang University School of Medicine between July 2012 to July 2014 were retrospectively reviewed. The factors related to pregnancy outcomes were analyzed by univariate and logistic regression methods. The clinical pregnancy rates in women with different age and different number of embryos transferred were compared. The clinical outcomes of stimulation with gonadotropin releasing hormone (GnRH) agonist long protocol, GnRH agonist short protocol and GnH antagonist protocol were evaluated in secondary infertile patients aged ≥ 40 years., Results: Among 1129 cycles, 376 cases (33.30%) had clinical pregnancy and 753 cases (66.70%) had no clinical pregnancy. There were significant differences in age, body mass index, basal follicle-stimulating hormone level, antral follicle number,paternal age and number of embryos transferred between pregnancy and no pregnancy groups (P<0.05); while only maternal age (OR=0.900, 95% CI: 0.873~0.928, P<0.001) and the number of embryos transferred (OR=2.248, 95% CI: 1.906~2.652, P<0.001) were the independent factors affecting the clinical pregnancy outcome of IVF-ET. There was no significant difference in clinical pregnancy rate between women aged 30~40 years with two embryos transferred and those aged<30 years with two or three embryos transferred(P>0.05). There were no significances in clinical pregnancy rate among women aged ≥ 40 years using GnRH agonist long protocol,GnRH agonist short protocol and GnRH antagonist protocol for stimulation (P>0.05)., Conclusion: Maternal age and number of embryos transferred have independent effect on IVF-ET clinical pregnancy outcome of secondary infertile women. We suggest that no more than two embryos should be transferred for women in their thirties to minimize the risk of multiple pregnancy while still having an acceptable pregnancy rate. The pregnancy rate of patients over 40 years decreases significantly, and there is no difference in pregnancy rate by using GnRH agonist long protocol, GnRH agonist short protocol or GnRH antagonist protocol.

Study Question: In patients with recurrent miscarriages (RM) or recurrent implantation failure (RIF), does the maternal killer immunoglobulin-like receptor (KIR) haplotype have an impact on live birth rates per cycle after embryo transfer with the patient's own or donated oocytes?, Summary Answer: After double embryo transfer (DET) in patients with the maternal KIR AA haplotype, a significantly increased early miscarriage rate was observed when the patient's own oocytes were used, and a significantly decreased live birth rate per cycle after embryo transfer was observed when donated oocytes were used., What Is Already Known: Interactions between fetal HLA-C and maternal KIR influence placentation during human pregnancy. There is an increased risk of RM, pre-eclampsia or fetal growth restriction in mothers with the KIR AA haplotype when the fetus has more HLA-C2 genes than the mother., Study Design, Size and Duration: Between 2010 and 2014, we performed a retrospective study that included 291 women, with RM or RIF, who had a total of 1304 assisted reproductive cycles., Participants/materials, Setting, Methods: Pregnancy, miscarriage and live birth rates per cycle after single or DET, categorized by the origin of the oocytes and the presence of maternal KIR haplotypes, were studied. KIR haplotype regions were defined by the presence of the following KIR genes: Cen-A/2DL3; Tel-A/3DL1 and 2DS4; Cen-B/2DL2 and 2DS2; as well as Tel-B/2DS1 and 3DS1., Main Results and the Role of Chance: Higher rates of early miscarriage per cycle after DET with the patient's own oocytes in mothers with the KIR AA haplotype (22.8%) followed by those with the KIR AB haplotype (16.7%) compared with mothers with the KIR BB haplotype (11.1%) were observed (P = 0.03). Significantly decreased live birth rates per cycle were observed after DET of donated oocytes in mothers with the KIR AA haplotype (7.5%) compared with those with the KIR AB (26.4%) and KIR BB (21.5%) haplotypes (P = 0.006). No statistically significant differences were observed for pregnancy, miscarriage and live birth rates per cycle among those with maternal KIR AA, AB and BB haplotypes after single embryo transfer (SET) with the patient's own or donated oocytes. The large number of cases studied strengthens the results and provides sufficient power to the statistical analysis., Limitations, Reasons for Caution: During the IVF procedure, DET induces the expression of more than one paternal HLA-C and the oocyte-derived maternal HLA-C in the oocyte-donation cycles probably behaves like paternal HLA-C. Because this was a retrospective study, we did not have data about the HLA-C of the parent, donor, chorionic villi, or infant, which is a limitation because we cannot show differences according to paternal or oocyte donor HLA-C1 and HLA-C2., Wider Implications of the Findings: These new insights could have an impact on the selection of SET in patients with RM or RIF, and a KIR AA haplotype. Also, it may help in oocyte and/or sperm donor selection by HLA-C in patients with RM or RIF and a KIR AA haplotype., Study Funding/competing Interests: No funding was received for this study. The authors have no conflicts of interest to declare., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To study the efficiency of letrozole, an aromatase inhibitor, in endometrial preparation for cryopreserved-thawed embryo transfer (FET) in women with polycystic ovarian syndrome (PCOS)., Design: Retrospective observational study., Patients: One hundred and twenty patients with PCOS who met the inclusion criteria for the study., Measurements: We assessed in vitro fertilization outcomes in one hundred and twenty patients with PCOS (148 cycles) who were prepared for and underwent FET between June 2011 and December 2012. Patients were prepared for FET using artificial hormone cycles induced with oestrogen and progesterone supplementation (n = 76), letrozole stimulation (n = 40) or hMG stimulation (n = 32)., Results: There were no differences in demographic characteristics between the groups, except that the letrozole group had a higher incidence of embryo transfer failure in the past. The letrozole stimulation group had a significantly higher maximal endometrial thickness and significantly higher rates of clinical pregnancy per transfer, ongoing pregnancy per transfer and implantation, compared with the artificial and hMG stimulation groups. Differences in these parameters between the artificial and hMG stimulation groups were not significant., Conclusion: Using letrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in patients with PCOS may be associated with better outcomes than using hormonal manipulation or hMG stimulation., (© 2013 John Wiley & Sons Ltd.)

Objective: To determine how often trophectoderm biopsy and rapid, real-time quantitative polymerase chain reaction (PCR)-based comprehensive chromosome screening (CCS) alters clinical management by resulting in the transfer of a different embryo than would have been chosen by traditional day 5 morphology-based criteria., Design: Prospective., Setting: Academic center for reproductive medicine., Patient(s): Infertile couples (n = 100; mean age 35 ± 4 years) with at least two blastocysts suitable for biopsy on day 5., Intervention(s): Prior to trophectoderm biopsy for CCS the embryologist identified which embryo would have been selected for traditional day 5 elective single ET., Main Outcome Measure(s): The risk of aneuploidy in the embryos that would have been selected on day 5 was calculated and compared with the aneuploidy rate of the cohort of all embryos that underwent CCS testing. The aneuploidy risk was compared between age groups., Result(s): After quantitative PCR-based CCS, 22% (95% confidence interval 15%-31%) of the embryos selected by day 5 morphology were aneuploid, which was lower than the 32% aneuploidy rate of the cohort. Patients ≥35 years had a higher risk of an aneuploid blastocyst being selected by morphology than those <35 years old (31% vs. 14%). Among patients who had selection altered by CCS, 74% (14/19) delivered, including 77% (10/13) after elective single ET. Most patients (77%) had an additional euploid blastocyst vitrified for future use., Conclusion(s): The CCS results alter embryo selection due to the presence of aneuploidy in embryos with optimal day 5 morphology. Excellent outcomes were obtained when CCS-based selection was different than morphology-based selection., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Infertility is a major problem in Nigeria, which has caused many couples to be burdened with physical, psychological and social issues. IVF (In-vitro fertilization) has played a major role in reducing the burden among infertile couples. However, despite the role of IVF in solving infertility in Nigeria, it is important to address the issue of rising rates of multiple births from IVF. Also to create a balance between the number of embryo transferred and easing the burden couples face from infertility., Objective: To determine the trend/rate in multiple gestations from IVF, identify possible factors responsible and proffer ways to reduce multiple gestation rates., Methods: We did a case series review from 2009-2011 of IVF cycles performed at a private clinic with an academic setting in Nigeria. Our primary outcome of interest was multiple gestations/pregnancies All patients identified with outcome of interest, were included in the study sample. We reviewed the IVF process of each patient using medical records from pre-evaluation to clinical pregnancy confirmed by ultrasound. We reported the multiple gestation trend/rate., Results: 25 women with the mean age of 39.9 +/- 7.3 years had multiple pregnancies from 2009 to 2011. Of the 25 women, 24% of the pregnancies, occurred in 2009, 40% occurred in 2010 and 36% in 2011. In 2009, 83% of the pregnancies were twin gestations and 17% triplets. In 2010, 40% were twin gestations, while triplet, quadruplet and quintuplet gestations were 20% each. In 2011, 66% were twin gestations and 34% quadruplet gestation. The factors we identified that could have lead to an increase in multiple gestations from 2009-2010 included improvement in pre-evaluation work up, stimulation protocol, efficacy of the IVF lab and mean of 5 embryos transferred. In 2011, embryo transferred was reduced to 3-4. From 2009 to 2011, mean number of embryos transferred was 4.2 (95% CI: 3.87-4.47)., Conclusion: Multiple gestations and associated risk from IVF in Nigeria can be reduced by reduction in number of embryos transferred and possibly by improvement in practice process. As the IVF process becomes more efficacious, fertility centres in Nigeria will not need to transfer up to 4 embryos in order to have a positive pregnancy; and as a result they can move towards two to single embryo transfer.

The aim of the study was to evaluate the efficacy of melatonin administration on oocyte quality in women underwent in vitro fertilization (IVF) cycles. Eighty-five women undergoing IVF cycles were randomized in two groups during IVF-embryo transfer (ET) procedure, 40 women with melatonin treatment (A) and 45 women without melatonin treatment (B). Primary endpoint was the number of morphologically mature oocytes retrieved (MII oocytes). Secondary endpoints were fertilization rate per number of mature oocytes, embryo quality and pregnancy rate. There were no differences between two groups according to age, and peak estradiol levels. The mean number of oocytes (15.33 vs. 14.27) and the mean number of mature oocytes did not differ between the two groups (12.63 vs. 10.94), whereas the percentage of mature oocytes (M2/oocytes retrieved) was significantly different in melatonin-treated group (p < 0.05). Fertilization rate (72.75 vs. 71.16) did not differ between the two groups. The mean number of class 1 embryos resulted higher in the group A (3.28 vs. 2.53) (p < 0.05). Clinical pregnancy rate was in tendency higher in the group treated with melatonin, although the differences did not reach statistical significance. Melatonin is likely to improve oocyte and embryo quality in women undergoing IVF or intracytoplasmic sperm insemination (ICSI).

Background: Endometrial cavity fluid (ECF) is a fluid accumulation within the endometrial cavity. The significance of ECF remains unclear during the program of in vitro fertilization-embryo transfer (IVF-ET). The aim of the present study was to investigate the associated factors to ECF, visualized through ultrasound at the day of oocyte retrieval, and the relevant impact on the outcome of IVF-ET., Methods: From the clinical data of 1557 infertility patients for IVF-ET program, 46 ECF patients were retrospectively selected as the ECF group; and another 134 patients with a bilateral salpingectomy and without ECF, selected as the control group. The demographics and the outcome of IVF-ET were compared between the two groups., Results: The incidence of ECF was 2.95% (46/1557). Over half (28/46, 60.87%) of ECF patients had tubal infertility. Only 12 Of 46 ECF patients (26.09%) had visible hydrosalpinx on ultrasonography before ovarian stimulation. The cycle cancellation rate (4/46, 8.69%) of ECF group was not significantly higher than that of the control group (6/134, 4.48%; P > 0.05). Reasons for cycle cancellation in both groups were all the high risk of ovarian hyperstimulation syndrome (OHSS). No significant difference was found in clinical pregnancy rate between the patients with their ECF <3.5 mm in the anterior-posterior diameter (APD) and the control group (35.48% versus 30.47%; P > 0.05). No clinical pregnancy was found among those patients with their ECF equal or higher 3.5 mm in APD., Conclusions: It was tubal infertility, not hydrosalpinx, which was related to the development of ECF. Excessive ECF (equal or higher 3.5 mm in APD) at the day of oocyte retrieval would have a negative impact on the outcome of IVF-ET.

Objective: To report an unusual case of congenital cervical atresia and tubal factor infertility, achieving triplet pregnancy through transmyometrial embryo transfer (ET) resulting in the delivery of healthy twins after multifetal pregnancy reduction (MFPR)., Design: Case report and literature review., Setting: University hospital., Intervention(s): Controlled ovarian hyperstimulation, oocyte retrieval, in vitro fertilization, transmyometrial ET, MFPR procedure for triplet pregnancy., Patient(s): A 33-year-old patient with endometriosis-associated and tubal factor infertility who underwent uterovaginal canalization surgery for congenital cervical atresia 9 years ago., Main Outcome Measure(s): Successful delivery after transmyometrial ET followed by MFPR., Result(s): A total of three IVF cycles and four procedures of transmyometrial ET were performed. In the third cycle a triplet pregnancy was achieved. MFPR was performed 35 days after embryos transfer, two healthy babies delivered at 31 weeks gestation., Conclusion(s): With aggressive therapy, successful pregnancy is possible in similar patients.

A retrospective analysis of clinical and laboratory data was made of all in-vitro fertilization (IVF) patients with tubal pathology who had their first ever embryo transfer cycle between January 1st, 1992 and September 1st, 1996. The aim of the study was to determine the effect of the presence of a hydrosalpinx, whether or not visible by ultrasound, on pregnancy, multiple pregnancy and implantation rates in our patient population. The IVF success rate was also analysed by calculating cumulative ongoing pregnancy rates of the same patient group using the lifetime table approach. In the presence of an ultrasound-visible hydrosalpinx, rates of pregnancy and multiple pregnancy appeared reduced, but the differences were not significant. The rates of implantation, clinical implantation and ongoing implantation were significantly lower in the presence of an ultrasound-visible hydrosalpinx (odds ratios 0.33-0.46, C.I. 0.21-0.96). The cumulative chance of achieving an ongoing pregnancy after one or more IVF cycles was significantly reduced in the presence of an ultrasound-visible hydrosalpinx (relative hazard 0.36, C.I. 0.22-0.59). In the presence of a hydrosalpinx not visible by ultrasound the IVF outcome was not reduced. This retrospective study confirms that patients with hydrosalpinges have an impaired IVF outcome. Unique to this study and previously unobserved is the finding that there is a subgroup of patients with hydrosalpinges, those with ultrasound-visible hydrosalpinges, which is exclusively responsible for this impaired outcome.

Purpose: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program., Methods: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/ mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed., Results: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0.004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups., Conclusions: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.

Because the process of conception is affected by many variables, a multiple logistic regression analysis was performed to assess (i) the impact and relative weight of both patient and embryo variables and (ii) their possible effects on the probability of a vital pregnancy after embryo transfer. A statistical model was constructed predicting the probability of pregnancy after embryo transfer. The variables that contributed significantly to the predictive value of the model were the age of the patient, the cause of infertility, the number of embryos transferred and the average morphology score of the transferred embryos. Embryo variables appeared to have a significant but modest value in predicting the probability of pregnancy after embryo transfer. Other variables, such as the thickness of the endometrium, were found to have no prognostic value. Moreover, we found that their effect could be explained by the variables already included in the model.

To assess the incidence of miscarriage, multiple pregnancy and outcome of pregnancy in relation to the number of embryos transferred during in-vitro fertilization (IVF), an analysis was performed of 1060 pregnancies conceived in a tertiary-referral IVF clinic. There was no difference in the miscarriage rate after transfer of one or two embryos (37.7% and 34.6%), or after three or four embryos (22.5% and 25.2%). The miscarriage rate was, however, higher when one or two embryos were transferred compared with three (P < 0.01) or four embryos (P < 0.02). Of the 724 ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%) twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean (+/- SD) ages of women with singleton, twin, triplet and quadruplet pregnancies were 32.5 (+/- 3.8), 32.0 (+/- 3.5), 29.76 (+/- 4.3) and 29.67 (+/- 2.5) years respectively. The mean age of women with singleton and twin pregnancies was similar and both were greater than that of triplet pregnancies (P < 0.007). The overall perinatal mortality rate (PNMR) was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins 80.0/1000 and for triplets 30.6/1000. All of the babies from the three quadruplet pregnancies survived. There were more babies lost in the twin pregnancies than any other group, although this only reached significance for singletons versus twins (P < 0.00005). We conclude that the incidence of miscarriage is increased in women in whom one or two embryos are transferred. Multiple pregnancies are more likely to occur in younger women and are associated with a significantly higher rate of perinatal mortality.