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BACKGROUND During the human menstrual cycle and pregnancy, the endometrium undergoes a series of dynamic remodeling processes to adapt to physiological changes. Insufficient endometrial remodeling, characterized by inadequate endometrial proliferation, decidualization and spiral artery remodeling, is associated with infertility, endometriosis, dysfunctional uterine bleeding, and pregnancy-related complications such as preeclampsia and miscarriage. Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor-β (TGF-β) superfamily, are multifunctional cytokines that regulate diverse cellular activities, such as differentiation, proliferation, apoptosis, and extracellular matrix synthesis, are now understood as integral to multiple reproductive processes in women. Investigations using human biological samples have shown that BMPs are essential for regulating human endometrial remodeling processes, including endometrial proliferation and decidualization. OBJECTIVE AND RATIONALE This review summarizes our current knowledge on the known pathophysiological roles of BMPs and their underlying molecular mechanisms in regulating human endometrial proliferation and decidualization, with the goal of promoting the development of innovative strategies for diagnosing, treating and preventing infertility and adverse pregnancy complications associated with dysregulated human endometrial remodeling. SEARCH METHODS A literature search for original articles published up to June 2023 was conducted in the PubMed, MEDLINE, and Google Scholar databases, identifying studies on the roles of BMPs in endometrial remodeling during the human menstrual cycle and pregnancy. Articles identified were restricted to English language full-text papers. OUTCOMES BMP ligands and receptors and their transduction molecules are expressed in the endometrium and at the maternal–fetal interface. Along with emerging technologies such as tissue microarrays, 3D organoid cultures and advanced single-cell transcriptomics, and given the clinical availability of recombinant human proteins and ongoing pharmaceutical development, it is now clear that BMPs exert multiple roles in regulating human endometrial remodeling and that these biomolecules (and their receptors) can be targeted for diagnostic and therapeutic purposes. Moreover, dysregulation of these ligands, their receptors, or signaling determinants can impact endometrial remodeling, contributing to infertility or pregnancy-related complications (e.g. preeclampsia and miscarriage). WIDER IMPLICATIONS Although further clinical trials are needed, recent advancements in the development of recombinant BMP ligands, synthetic BMP inhibitors, receptor antagonists, BMP ligand sequestration tools, and gene therapies have underscored the BMPs as candidate diagnostic biomarkers and positioned the BMP signaling pathway as a promising therapeutic target for addressing infertility and pregnancy complications related to dysregulated human endometrial remodeling. [ABSTRACT FROM AUTHOR]

Background: Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer.Methods: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405.Findings: 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029).Interpretation: Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies.Funding: The National Key Research and Development Program of China. [ABSTRACT FROM AUTHOR]

Study Question: Are meiotic segregation patterns of reciprocal translocations affected by the combined effect of chromosome type and carrier's sex?Summary Answer: Interaction of an acrocentric chromosome (Acr-ch) involved in the translocation and sex of the carrier influences the proportion of alternate segregation for normal or balanced chromosome contents during meiotic segregation in autosomal reciprocal translocations.What Is Known Already: Carriers of reciprocal translocations are at a significantly increased risk of fertility problems due to the generation of unbalanced gametes in meiotic segregation of a quadrivalent. Previous studies have reported that meiotic segregation patterns of a quadrivalent can be affected by factors such as a carrier's sex and age and the chromosome type. However, the reported proportion of alternate segregation does not differ significantly, except in one study, and whether combined effects between these factors exist is unclear.Study Design, Size, Duration: A retrospective study of array comparative genomic hybridization (aCGH) outcome data from patients with autosomal reciprocal translocations was conducted to analyse meiotic segregation patterns and blastocyst euploidy rates. We enroled 473 couples whose embryos were tested between January 2013 and September 2016.Participants/materials, Setting, Methods: Meiotic segregation patterns of 2101 blastocysts from 243 female carriers, including 76 cases with translocations involving Acr-ch, and 230 male carriers, including 88 cases with translocations involving Acr-ch, were analysed according to chromosome type, carrier's sex and age.Main Results and the Role Of Chance: In cases with translocations involving the Acr-ch subgroup, the proportion of alternate segregation (53.9 vs 33.4%, P < 0.0001) was significantly higher in male carriers than in female carriers, with the proportion of 3:1 segregation (6.8 vs 16.3%, P < 0.0001) being significantly lower. The proportions of alternate segregation were similar between sexes in cases with translocations not involving the Acr-ch subgroup. Meanwhile, in the female carrier subgroup, the proportion of alternate segregation (33.4 vs 45.2%, P < 0.001) was significantly lower and the proportion of 3:1 segregation (16.3 vs 8.2%, P < 0.001) was significantly higher in cases with translocations involving Acr-ch than in those not. In the male carrier subgroup, the proportion of alternate segregation (53.9 vs 46.9%, P = 0.031) was higher and the proportion of adjacent-1 segregation (27.1 vs 37.3%, P < 0.001) was significantly lower in cases with translocations involving Acr-ch than in those not. Carrier's age did not affect the meiotic segregation patterns. However the euploidy rates were significantly lower in couples with advanced compared to young maternal age respectively.Limitations, Reasons For Caution: Mosaic embryos were not identified using aCGH in this study. Patients with complex chromosome rearrangements and translocations involving sex chromosomes were excluded. Interchromosomal effect was not analysed.Wider Implications Of the Findings: The findings of this study provide detailed information for genetic counselling of couples with autosomal reciprocal translocations on their chances of producing euploid gametes.Study Funding/competing Interest(s): This research was supported by the National Key Research and Development Program of China (2016YFC1000202); the National Natural Science Foundation of China (81671522); the Natural Science Foundation of Shandong Province in China (ZR2016HP09); and the Innovative Foundation of Reproductive Hospital Affiliated to Shandong University (20171114, 20171111). No competing interests are declared.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Purpose: Mosaicism is a prevalent characteristic of human preimplantation embryos. This retrospective cohort study aimed to investigate pregnancy outcomes after transfer of mosaic or euploid embryos.Methods: The embryos, which had been transferred as "euploidy," were processed using array-based comparative genomic hybridization (aCGH). The original aCGH charts of the transferred embryos were reanalyzed. Mosaic and control euploid embryos were defined according to log2 ratio calls.Results: Overall, 102 embryos were determined to be mosaic, of which 101 were estimated to harbor no more than 50% aneuploid mosaicism. Additionally, 268 euploid embryos were matched as controls. The rates of live birth (46.6% vs. 59.1%, odds ratio (OR) 0.60, 95% confidence interval (CI) 0.38-0.95), and biochemical pregnancy (65.7% vs. 76.1%, OR 0.60, 95% CI 0.37-0.99) per transfer cycle were significantly lower after mosaic embryo transfer than after euploid embryo transfer. The rates of clinical pregnancy and pregnancy loss and the risks of obstetric outcomes did not differ significantly between the two groups.Conclusions: Compared with euploid embryo transfer, mosaic embryo transfer is associated with a lower rate of live birth, which is mainly attributed to a decreased rate of conception. However, as mosaic embryo transfer yielded a live birth rate of 46.6%, patients without euploid embryos could be counseled regarding this alternative option. [ABSTRACT FROM AUTHOR]

In 2013, consensus was reached that the preferred primary outcome of all infertility treatment trials is the live birth rate or cumulative live birth rate [[1]]. Smith et al. [[2]] compared a segmented versus non-segmented in vitro fertilization (IVF) cycle with the primary outcome of cumulative live birth, an important outcome to comprehensively assess the effectiveness of an IVF cycle [[3]]. 6 Polyzos NP, Drakopoulos P, Parra J. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including approximately 15,000 women. 7 Zaca C, Bazzocchi A, Pennetta F, Bonu MA, Coticchio G, Borini A. Cumulative live birth rate in freeze-all cycles is comparable to that of a conventional embryo transfer policy at the cleavage stage but superior at the blastocyst stage. [Extracted from the article]

Objective: To evaluate the effect of frozen embryo transfer on maternal and neonatal complications of singleton and twin pregnancies compared with fresh embryo transfer in women with polycystic ovary syndrome (PCOS).Design: A secondary analysis of a multicenter, randomized, controlled trial comparing live birth after frozen vs. fresh embryo transfer (FreFro-PCOS).Setting: Reproductive medicine centers.Patient(s): A total of 1,508 patients with a diagnosis of PCOS who were undergoing IVF were enrolled.Intervention(s): On day of oocyte retrieval, eligible patients were randomized to the fresh or frozen embryo transfer groups. Up to two embryos were transferred in both groups. All pregnancies were followed up until delivery.Main Outcome Measure(s): Gestational diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and large for gestational age.Result(s): The risks of gestational diabetes mellitus, preterm birth, and small for gestational age were comparable between the frozen and fresh embryo transfer groups in both singleton and twin births. However, singleton infants born after frozen embryo transfer were more likely to be large for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval 1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%; relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after fresh embryo transfer.Conclusion(s): In women with PCOS, frozen embryo transfer resulted in an increased risk of large for gestational age in singleton pregnancy and a higher risk of pre-eclampsia in twin pregnancy.Clinical Trial Registration Number: NCT01841528. [ABSTRACT FROM AUTHOR]

Randomized controlled trials and intent-to-treat analyses are important for infertility clinical studies. Dropouts or crossovers during the study process will disrupt the randomization design and affect the intent-to-treat analysis. In this review, we have briefly introduced the occurrence of dropout and crossover from our previous Reproductive Medicine Network and other related studies and provided some experience obtained from these studies on how to minimize and reduce the occurrence of dropout and crossover for infertility randomized clinical studies. [ABSTRACT FROM AUTHOR]

We found that the frequency of livebirths in the frozen embryo transfer group after the first frozen embryo transfer was 439 (53%) of 825, whereas the proportion of livebirths in the fresh embryo transfer group after the fresh and the first frozen embryo transfer was 546 (66%) of 825 (p=0-0001). Roque and colleagues proposed that a programmed regimen for endometrial preparation could contribute to the increased risk of pre-eclampsia after frozen embryo transfer. RSL reports grants from NIH and Guerbet, grants and consultancy fees from Ferring, and consultancy fees from Bayer, AbbVie, Fractyl, and Ogeda, outside of the submitted work. [Extracted from the article]

STUDY QUESTION Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11–12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): −2.6%; 95% CI: −9.0% to 3.8%, P- value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: −6.4%; 95% CI: −12.6% to −0.1%, P -value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE May 2018. DATE OF FIRST PATIENT'S ENROLMENT November 2018. [ABSTRACT FROM AUTHOR]

Embryo transfer, one of the most essential procedures in assisted reproductive technology, plays a vital role in the success of in-vitro fertilization and intracytoplasmic sperm injection. During the last decades, the strategies for embryo transfer have changed dramatically. In this review, we evaluate the efficacy and safety of several current embryo transfer strategies including fresh versus frozen embryo transfer, cleavage- versus blastocyst-stage embryo transfer, and single- versus double-embryo transfer. Available evidence indicates that the freeze-only strategy improves the live birth rate after the first embryo transfer in high responders while making no difference in normal responders. The risk of ovarian hyperstimulation syndrome is significantly reduced in the freeze-only strategy. Fresh blastocyst-stage embryo transfer increased live birth rate compared to cleavage-stage embryo transfer. The best embryo transfer strategy is one which tailors to individual circumstances and preferences. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. Methods: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously reported PE biomarkers [including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A] were measured in 34 women diagnosed with PE and 34 matched normotensive controls. Results: The PE group has significantly higher first-trimester serum levels of interleukin (IL)-2Rα, IL-9, tumor necrosis factor-β (TNF-β), RANTES, hepatocyte growth factor (HGF), total IgM, and total IgG, and aPS IgG optical density (OD) value, as well as lower first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value than the control group. Combining top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI) 0.983 (0.952–1.000), with a sensitivity of 100% and a specificity of 94.1%] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI 0.825 (0.726–0.924) and 0.670 (0.539–0.800), respectively]. Conclusion: We identified novel first-trimester serum biomarkers and developed an effective first-trimester prediction model using immune-related factors and PlGF for PE, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. Methods: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously reported PE biomarkers [including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A] were measured in 34 women diagnosed with PE and 34 matched normotensive controls. Results: The PE group has significantly higher first-trimester serum levels of interleukin (IL)-2Rα, IL-9, tumor necrosis factor-β (TNF-β), RANTES, hepatocyte growth factor (HGF), total IgM, and total IgG, and aPS IgG optical density (OD) value, as well as lower first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value than the control group. Combining top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI) 0.983 (0.952–1.000), with a sensitivity of 100% and a specificity of 94.1%] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI 0.825 (0.726–0.924) and 0.670 (0.539–0.800), respectively]. Conclusion: We identified novel first-trimester serum biomarkers and developed an effective first-trimester prediction model using immune-related factors and PlGF for PE, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE. [ABSTRACT FROM AUTHOR]

Objective: To study the association between two single-nucleotide polymorphisms (SNPs) variants (rs2241766 and rs1501299) of the adiponectin gene (ADIPOQ) and polycystic ovary syndrome (PCOS) in PCOS family trios. Design: Family-based study. Setting: University hospital. Patient(s): A total of 224 unrelated PCOS probands, their biologic parents, and 204 control subjects. Intervention(s): Anthropometric, hormonal, and metabolic assessment; genotype detection. Main Outcome Measure(s): Basic endocrine, serum fasting glucose (FG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels were measured. The transmission disequilibrium test (TDT) was used to analyze the association between two SNPs of ADIPOQ and PCOS. Result(s): A significant positive association was detected between SNP rs1501299 and PCOS. Compared with AA genotype, AC and CC genotypes had increased risk for PCOS, and the difference remained significant after adjustment for age, body mass index, and testosterone (T). The levels of T, TG, HDL cholesterol, and FINS were significantly higher in obese PCOS patients. However, we failed to find significant overtransmission of the other SNP, rs2241766, from parents to PCOS offspring. The genotype frequencies of rs2241766 and rs1501299 were not different in obese and lean PCOS patients and their parents. Conclusion(s): TDT confirms that SNP rs1501299 in the ADIPOQ is significantly associated with the risk of PCOS in the Chinese Han population. The present data may provide a basis for further studies of the role of the ADIPOQ in the etiology of PCOS. [Copyright &y& Elsevier]

Background: Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen-thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer.Methods/design: This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen-thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test.Discussion: We hypothesize that elective embryo cryopreservation and frozen-thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy.Trial Registration: ClinicalTrials.gov Identifier: NCT01841528. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the use of 10 mg of prednisone, compared with placebo, improve the chances of achieving live birth among women with recurrent implantation failure? Findings: In this randomized clinical trial that included 715 women who had experienced 2 or more unsuccessful embryo transfer cycles, the live birth rate was 37.8% among women who received 10 mg of prednisone vs 38.8% among women who received placebo, a nonsignificant difference. Meaning: The findings do not support the routine use of 10 mg of prednisone in women with recurrent implantation failure. Importance: Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. Objective: To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. Design, Setting, and Participants: A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Interventions: Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. Main Outcomes and Measures: The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Results: Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, −1.0% [95% CI, −8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P =.78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P =.04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P =.04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Conclusions and Relevance: Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800018783 This randomized clinical trial evaluates whether the administration of prednisone would increase the rate of live birth in women with recurrent implantation failure. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether the risks of early- or late-onset preeclampsia vary among frozen embryo transfer (FET) with different regimens for endometrial preparation and fresh embryo transfer (FreET). Methods: We retrospectively included a total of 24129 women who achieved singleton delivery during their first cycles of in vitro fertilization (IVF) between January 2012 and March 2020. The risks of early- and late-onset preeclampsia after FET with endometrial preparation by natural ovulation cycles (FET-NC) or by artificial cycles (FET-AC) were compared to that after FreET. Results: After adjustment via multivariable logistic regression, the total risk of preeclampsia was higher in the FET-AC group compared to the FreET group [2.2% vs. 0.9%; adjusted odds ratio (aOR): 2.00; 95% confidence interval (CI): 1.45–2.76] and FET-NC group (2.2% vs. 0.9%; aOR: 2.17; 95% CI: 1.59–2.96).When stratified by the gestational age at delivery based on < 34 weeks or ≥ 34 weeks, the risk of late-onset preeclampsia remained higher in the FET-AC group than that in the and FreET group (1.8% vs. 0.6%; aOR: 2.56; 95% CI: 1.83–3.58) and the FET-NC group (1.8% vs. 0.6%; aOR: 2.63; 95% CI: 1.86–3.73). We did not find a statistically significant difference in the risk of early-onset preeclampsia among the three groups. Conclusions: An artificial regimen for endometrial preparation was more associated with an increased risk of late-onset preeclampsia after FET. Given that FET-AC is widely used in clinical practice, the potential maternal risk factors for late-onset preeclampsia when using the FET-AC regimen should be further explored, considering the maternal origin of late-onset preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating studies have suggested singletons born after frozen embryo transfer (FET) were higher than those born after fresh embryo transfer (Fre‐ET). However, fewer studies had investigated the gestational age‐specific between‐group difference in birthweight. This study aimed to investigate the gestational week‐specific difference in singleton birthweight after FET vs Fre‐ET and explore potential factors that impact the difference. Material and methods: In this retrospective cohort study, a total of 25 863 singletons were included. Multivariable linear regression and logistic regression were used to evaluate the between‐group differences in mean birthweight and the incidences of large for gestational age (LGA) and small for gestational age (SGA), respectively. Results: Multivariable regression analyses showed a statistically significant interaction between types of embryo transfer (ie FET vs Fre‐ET) and the gestational week on mean birthweight (P < 0.001) and on the risks of large for gestational age (P = 0.001) and small for gestational age (P < 0.001). When stratified by gestational week, the differences in mean birthweight and the risks of LGA and SGA were only observed in singletons born at 37 gestational weeks or later. After adjusting for confounders, full‐term but not preterm singletons born after FET had a higher birthweight (3497.58 ± 439.73 g vs 3445.67 ± 450.24 g; adjusted mean difference 58.35 g; 95% confidence interval [CI] 38.72–77.98 g), a higher risk of LGA (24.3% vs 21.1%; adjusted odds ratio [OR] 1.28, 95% CI 1.15–1.42) and a lower risk of SGA (3.1% vs 4.8%; adjusted OR 0.61, 95% CI 0.53–0.70) compared with those born after Fre‐ET. Conclusions: The differences in birthweight between FET and Fre‐ET were observed in full‐term singletons but not preterm singletons. [ABSTRACT FROM AUTHOR]

Which factors are associated with the risk of clinical pregnancy loss in women with polycystic ovary syndrome (PCOS) undergoing IVF? Case–control study nested in a multicentre randomized trial comparing live birth rates between fresh and frozen embryo transfer in women with PCOS. Women with the outcome of clinical pregnancy loss were selected as the case group, those with live birth as the control group. Parameters before IVF treatment and variables during ovarian stimulation and embryo transfer were compared. Women with clinical pregnancy loss had higher maternal body mass index (BMI, P = 0.010), anti-Müllerian hormone (AMH, P = 0.032), 2-h glucose concentration after 75 g oral glucose tolerance test (OGTT, P = 0.025), and a higher proportion of fresh embryo transfers (P = 0.001). There were significant interactions between the types of transfer and antral follicle count (AFC, P = 0.013), 2-h glucose concentration after OGTT (P = 0.024) on clinical pregnancy loss in PCOS, indicating that these factors may have different effects on pregnancy loss after fresh versus frozen embryo transfer. When the multivariable logistic regression analysis was stratified by the fresh or frozen embryo transfer, AFC (adjusted odds ratio [aOR] 1.03, 95% confidence interval [CI] 1.01–1.05) was a risk factor for clinical pregnancy loss after fresh embryo transfer, while 2-hour glucose concentration after OGTT (aOR 1.13, 95% CI 1.01–1.25) was associated with clinical pregnancy loss in frozen embryo transfer (FET) cycles. In women with PCOS, fresh embryo transfer, higher BMI, AFC and 2-h glucose concentration after OGTT were risk factors for clinical pregnancy loss. FET may be a better choice to decrease the risk of clinical pregnancy loss, especially for those with higher AFC. During FET, 2-h glucose after OGTT appears to be associated with clinical pregnancy loss and warrants close monitoring. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the between-group difference in singleton birth weight following frozen vs. fresh embryo transfer varied with infant sex.Design: A post hoc exploratory secondary analysis of data from three multicenter randomized trials compared the live birth rates between freeze-only vs. fresh embryo transfer.Setting: Academic fertility centers.Patient(s): A total of 1,886 women who achieved singleton live birth after a frozen or fresh embryo transfer during these trials were included.Intervention(s): Women underwent either a frozen or fresh embryo transfer.Main Outcome Measure(s): Mean birth weight, large for gestational age (LGA), and small for gestational age (SGA).Result(s): There was an interaction between the types of embryo transfer and infant sex on the birth weight and on the incidences of LGA and SGA. Among male infants, compared with singletons following fresh embryo transfer, singletons following frozen embryo transfer had higher mean birth weights (3,520.6 ± 526.1 vs. 3,345.1 ± 524.9 g), a higher risk of being LGA (25.2% vs. 15.7%), and a lower risk of being SGA (3.3% vs. 6.1%). However, among the female infants, no statistically significant difference was found in the mean birth weight (3,336.5 ± 514.8 vs. 3,299.5 ± 485.0 g) or the risks of being LGA (18.8% vs. 15.7%) or SGA (5.2% vs. 6.0%) between frozen and fresh embryo transfer.Conclusion(s): Male singletons born after frozen embryo transfer were more likely to have a higher birth weight than those born after fresh embryo transfer. [ABSTRACT FROM AUTHOR]

Introduction: Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer. Material and methods: We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze‐all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n = 191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n = 96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n = 1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth. Results: For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P =.009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P =.071). Conclusions: The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single‐blastocyst frozen embryo transfer. [ABSTRACT FROM AUTHOR]

Is there a difference in live birth rate between a freeze-only strategy and fresh embryo transfer, and what is the effect of varying progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration? A secondary analysis of data from three randomized trials comparing the live birth rate after elective frozen versus fresh embryo transfer, which respectively enrolled 1508 women with polycystic ovary syndrome, 2157 ovulatory women who underwent cleavage-stage embryo transfer and 1650 ovulatory women who underwent single blastocyst transfer. Women were randomly assigned to the frozen or fresh embryo transfer group in the original trials. The primary outcome was live birth rate after the initial embryo transfer. The live birth rate after a freeze-only strategy was consistently higher than fresh embryo transfer at any progesterone concentration on the day of HCG administration. Nonetheless, the between-group difference in live birth rate after frozen versus fresh embryo transfer was greater in women with progesterone concentrations ≥1.14 ng/ml (52.7% versus 37.3%, odds ratio (OR) 1.88, 95% confidence interval (CI) 1.55–2.27, P = 7.89 × 10–11) than in women with progesterone concentrations <1.14 ng/ml (53.3% versus 48.1%, OR 1.23, 95% CI 1.08–1.41, P = 0.002). In women with progesterone concentration ≥1.14 ng/ml, frozen embryo transfer also resulted in higher rates of conception and clinical pregnancy than fresh embryo transfer. In women with normal or high ovarian response, a freeze-only strategy resulted in a higher live birth rate than fresh embryo transfer, irrespective of progesterone concentration. Moreover, women with progesterone concentration ≥1.14 ng/ml may benefit more from a freeze-only strategy. [ABSTRACT FROM AUTHOR]

Study Question: Does the inheritance of polycystic ovary syndrome (PCOS) susceptibility single-nucleotide polymorphism affect the phenotype of offspring?Summary Answer: Male offspring who inherit PCOS-related genetic variations from PCOS mothers were more susceptible to developing the metabolic abnormality in their later life.What Is Known Already: Genetic factors are considered the major etiology of PCOS. Previous studies have highlighted that offspring of women with PCOS had an increased risk of the same disease or PCOS-like symptoms.Study Design, Size, Duration: The study involved 172 children born to women with PCOS and 529 children born to non-PCOS women. All offspring were conceived by assisted reproductive technologies.Participants/materials, Setting, Methods: The offspring ranged from 1 to 8 years old. Metabolic phenotype analyses were performed in offspring aged from 2 to 8 (N = 619). Sanger sequencing, TaqMan and Sequenom MassARRAY were used to sequence the samples.Main Results and the Role Of Chance: In male offspring, the fasting insulin (FINS) (P = 0.037) homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.038) and the homeostasis model assessment of pancreatic beta-cell function (HOMA-β) (P = 0.038) levels were higher in offspring of PCOS mothers compared to controls. In female offspring, PCOS offspring had a significantly higher anti-Müllerian hormone levels (P = 0.001) compared to those from control mothers. In male offspring of PCOS mothers, subjects with a T allele at rs2349415 in the gene FSHR had higher FINS (P = 0.023), HOMA-IR (P = 0.030) and HOMA-β levels (P = 0.013) than those in the homozygous CC group. The same increased trend in FINS, HOMA-IR and HOMA-β levels could be found in the CC and TC group in rs2268361 located in gene FSHR compared to the TT group (P = 0.029, P = 0.030, P = 0.046, respectively). As for rs10818854 in the DENND1A gene, the AA and AG group had a higher FINS (P = 0.037) and HOMA-β (P = 0.008) levels than the homozygous CC group.Limitations, Reasons For Caution: Firstly, the offspring may be too young to see any phenotype changes. Secondly, this study only analyzed the differences of genotype frequency using the dominant model instead of all three models due to the limited sample size of the homozygous model. The results, therefore, should be replicated and performed in a larger sample size population. Thirdly, environmental impacts cannot be ruled out.Wider Implications Of the Findings: The findings presented in this thesis add to our understanding the changes in offspring born to PCOS women and remind us to consider early intervention to avoid more severe effects.Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China 2017YFC1001000 (to Z.-J.C.), the National Natural Science Foundation of China 81430029 (to Z.-J.C.), 81622021 and 31571548 (to H.Z.), the National Natural Science Foundation of Shandong Province JQ201816 (to H.Z.) and Shandong Provincial Key Research and Development Program 2017G006036 (to L.-L.C.) and 2018YFJH0504 (to Z.-J.C.). There are no conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: The endometrial preparation during frozen embryo transfer (FET) can be performed by natural cycle (NC), hormone replacement therapy (HRT) cycle and cycle with ovulation induction (OI). Whether different FET preparation protocols can affect maternal and neonatal outcomes is still inconclusive. Methods: This was a retrospective cohort study that included 6886 women who delivered singleton live birth babies after 28 weeks of pregnancy underwent FET from January, 2015 to July, 2018. Women were divided into three groups according to the protocols used for endometrial preparation during FET: NC group (N = 4727), HRT group (N = 1642) and OI group (N = 517). Results: After adjusting for the effect of age, body mass index (BMI), irregular menstruation, antral follicle count (AFC), endometrial thickness, the levels of testosterone, anti-Müllerian hormone (AMH), preconceptional fasting glucose (PFG), systolic and diastolic pressure et al., the HRT group had higher risk of hypertensive disorders of pregnancy (HDP) compared with the NC group (adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.54–2.60). Singletons born after HRT FET were at increased risk of low birth weight (LBW) compared to NC group (aOR 1.49, 95%CI 1.09–2.06). The risks of preterm birth (PTB) in the HRT and OI group were elevated compared with the NC group (aOR 1.78, 95%CI 1.39–2.28 and aOR 1.51, 95%CI 1.02–2.23, respectively). Conclusions: The HRT protocol for endometrial preparation during frozen embryo transfer of blastocysts was associated with increased risk of maternal and neonatal complications, compared to the NC and OI protocol. [ABSTRACT FROM AUTHOR]

What are the factors associated with the increased incidence of pre-eclampsia in pregnancies conceived through IVF using autologous oocytes? A nested case–control study from the combined cohort of three multicentre randomized trials comparing fresh to frozen embryo transfer, including women who achieved clinical pregnancy after the first embryo transfer. Multivariable logistic regression was used to assess the effect of baseline characteristics, ovarian response parameters, type of fertilization, type of embryo transfer, and number of gestational sacs on the risk of pre-eclampsia. There were 2965 clinical pregnancies and 90 women were diagnosed with pre-eclampsia. Twin gestations (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.50–3.66), mean arterial pressure (OR 1.04, 95% CI 1.01–1.07), frozen embryo transfer (OR 2.06, 95% CI 1.27–3.35), body mass index (BMI) (OR 1.10, 95% CI 1.02–1.18), progesterone level on the day of human chorionic gonadotrophin trigger (OR 1.53, 95% CI 1.07–2.20), and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999–1.000, P = 0.037) were associated with the risk of pre-eclampsia. When the analysis was confined to women who underwent frozen embryo transfer, twin gestations (OR 2.44, 95% CI 1.43–4.18), BMI (OR 1.13, 95% CI 1.03–1.23) and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999–1.000, P = 0.014) were still related to the risk of pre-eclampsia. The embryo stage at transfer was not included in the final models. Frozen embryo transfer was an independent risk factor of pre-eclampsia in assisted reproductive technology. The high ovarian response may also increase the risk of pre-eclampsia. The embryo stage at transfer was not related to the risk of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Does oral contraceptive pretreatment impact IVF–embryo transfer cycle outcomes in women following the gonadotrophin-releasing hormone agonist (GnRHa) protocol? This retrospective study was designed to compare cycle outcomes after oral contraceptive pretreatment versus the standard protocol in women within the GnRHa long protocol or the GnRHa short protocol. A total of 2052 women undergoing their first IVF treatment with the GnRHa long protocol and 3557 women with the GnRHa short protocol between 2012 and 2017 were enrolled. No significant differences in the rates of clinical pregnancy (long protocol: 49.2% versus 46.7%; short protocol: 39.4% versus 38.0%) or live birth (long protocol: 44.3% versus 41.3%; short protocol: 32.8% versus 31.4%) after fresh embryo transfer were observed between the oral contraceptive group and the control group in either the long protocol or the short protocol. Oral contraceptive pretreatment has no effect on IVF outcomes in either the GnRHa long protocol or short protocol. [ABSTRACT FROM AUTHOR]

Background: Obese women have fewer oocytes retrieved, an increased cancelation rate, a higher miscarriage rate, and a lower live birth rate after assisted reproductive technology (ART) treatment compared with women with normal weight. Weight loss before ART treatment can significantly improve pregnancy rates and/or live births. An orlistat plus diet intervention could promote weight loss, but there is no evidence from randomized clinical trials evaluating the effect of orlistat preconceptional treatment on pregnancy outcome in overweight and obese women.Methods/design: We are conducting a multicenter, randomized placebo-controlled, double-blind clinical trial in overweight and obese women aged 20-40 years undergoing in-vitro fertilization and embryo transfer (IVF-ET) with or without intracytoplasmic sperm injection, to evaluate whether orlistat treatment for 1-3 months before IVF-ET can improve the live birth rate. The primary outcome is live birth.Discussion: The results of this study will provide evidence for the effect of preconceptional orlistat treatment on IVF outcome in overweight/obese women.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-17011629 . Registered on 11 June 2017. [ABSTRACT FROM AUTHOR]

Study Question: Is the total dose of exogenous gonadotropins associated with blastocyst aneuploidy or live-birth rates in PGS cycles in Chinese women?Summary Answer: The total dose of exogenous gonadotropins is not significantly associated with blastocyst aneuploidy or live-birth rates in PGS cycles in Chinese women.What Is Known Already: The administration of gonadotropins in ovarian stimulation leads to supraphysiological steroid concentrations compared with those seen during natural cycles. The rate of euploid blastocytes is negatively associated with female age.Study Design, Size, Duration: This is a retrospective study using anonymised data on PGS cycles performed in China from 2013 to 2017. Data from 1088 PGS cycles and 3219 embryos were analysed by array-comparative genomic hybridization (array-CGH).Participants/materials, Setting, Methods: The study included 944 women who underwent PGS cycles with COH. All cycles were analysed by the total dose of exogenous gonadotropins (<1500, 1500-3000 and >3000 IU), patient age (<35 and ≥35 y.o.) and number of oocytes retrieved (1-5, 6-10, 11-15 and >15 oocytes).Main Results and the Role Of Chance: In the group of younger women (<35 y.o., 537 PGS cycles), the incidence of aneuploidy ranged from 36.9 to 43.4% when data was stratified by gonadotropins dose. After adjusting for confounding factors, the dose of exogenous gonadotropins was not associated with the blastocyst aneuploidy rate. Similar results were shown in the group of women with advanced maternal age (≥35 y.o., 551 PGS cycles), with no difference in the rate of blastocyst aneuploidy among different gonadotropins dose groups (<1500 IU, 58.0%; 1500-3000 IU, 59.8%; and >3000 IU, 59.8%; P = 0.86). The live-birth rates after single cryopreserved blastocyst transfers were also not significantly associated with the gonadotropins dose.Limitations, Reasons For Caution: Limitations include the retrospective study design and the heterogeneity of the included patients. Additionally, array-CGH may not be able to correctly identify mosaicism.Wider Implications Of the Findings: The finding that gonadotropin dosage is not associated with embryonic aneuploidy or live-birth rates in Chinese women suggests that the high doses of gonadotropins used in ART cycles may be safe. The findings are consistent with those of prior studies in other populations.Study Funding/competing Interest(s): This study was supported by the National Natural Science Foundation of China (81671522) and National Key Research and Development Program of China (2016YFC1000202).Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Multiple pregnancies are one of the major safety concerns of in vitro fertilization (IVF) due to the increased risk of maternal and neonatal complications. Single embryo transfer is the most effective way to reduce the risk of multiple pregnancies. Selection of the embryo and optimization of the implantation environment are crucial to retain the success rate when the number of transferred embryos is diminished. Fresh embryo transfer with supra-physiological levels of hormones has been suggested to have an adverse effect on implantation. Elective frozen embryo transfer has been suggested to result in a higher rate of live birth than fresh embryo transfer. However, there is still a lack of evidence from randomized clinical trials comparing the efficacy and safety between frozen and fresh single blastocyst transfers.Methods/design: We are conducting a randomized controlled trial in women aged 20-35 undergoing their first cycle of IVF with or without intracytoplasmic sperm injection. After ovarian stimulation with a gonadotropin-releasing hormone antagonist protocol, women who obtain four or more embryos on day 3 of the embryo culture are randomized into two parallel groups: a single fresh blastocyst transfer group and a single frozen blastocyst transfer group (all blastocysts vitrified and a deferred frozen blastocyst transfer). The primary outcome is singleton live birth.Discussion: The results of this study will provide evidence for the efficacy and safety of the strategy of elective frozen single blastocyst transfer in women with a good prognosis.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-14005405 . Registered on 30 Oct 2014. [ABSTRACT FROM AUTHOR]

Study Question: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?Summary Answer: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.What Is Known Already: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.Study Design, Size, Duration: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.Participants/materials, Setting, Methods: At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.Main Results and the Role Of Chance: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.Limitations, Reasons For Caution: The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.Wider Implications Of the Findings: Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.Study Funding/competing Interests: This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.Trial Registration Number: Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. [ABSTRACT FROM AUTHOR]

This retrospective cohort study observed the live birth rates as well as cumulative live birth rates in women with poor ovarian response (POR) undergoing IVF–embryo transfer treatment, stratified for age and cycle number. Four hundred and one patients with POR diagnosed according to the Bologna criteria were enrolled and 700 IVF–ET cycles were analysed. The overall live-birth rate per cycle was 18.3%. From cycle 1 up to cycle 3, the live-birth rates decreased significantly from 22.2% to 11.1%. The live-birth rate fell to 2.4% in cycles 4 and over. When age advanced, the live birth rates decreased obviously ( P < 0.01): 30.0% for women <35 years old, 17.0% for those 35–40 years old, and 9.0% for women older than 40 years. Similarly, the cumulative live birth rates dropped from 48.0% (<35 years) to 16.9% (≥40 years) accordingly. Younger patients (<35 years old) with POR achieved better pregnancy results compared with patients of advanced age. Extremely low live-birth rates could be anticipated after three unsuccessful cycles; therefore it may not be appropriate to suggest more IVF cycles in POR women. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the direct genetic contribution of the polycystic ovary syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNPs), identified by previous genome-wide association studies (GWAS) to the definitive clinical features of the syndrome? SUMMARY ANSWER Each single PCOS clinical feature had a specific genetic association, and rs4385527 in the chromosome 9 open reading frame 3 (C9orf3) conferred a particular risk to the three defined PCOS clinical features in this study, which suggested its fundamental role in the etiology of PCOS. WHAT IS KNOWN ALREADY PCOS is a heterogeneous disorder characterized by anovulation (OA), hyperandrogenism (HA) and polycystic ovary morphology (PCOM). Two previous GWAS in China have identified 15 independent susceptibility SNPs related to PCOS (PCOS-SNPs). However, little is known about the candidate gene of each clinical feature. STUDY DESIGN, SIZE, DURATION Case–control study. Three independent groups of women were recruited from 2010 to 2012: 746 subjects with OA only, 278 subjects with HA only and 536 subjects with PCOM only. A total of 1790 healthy women with none of the above pathological characteristics were also enrolled as control subjects during the same time period. PARTICIPANTS/MATERIALS, SETTING, METHODS All participants were women of reproductive age. Genotype and allelic frequencies of 15 PCOS-SNPs were determined in all subjects using direct sequencing and Sequenom Arrays. The allelic frequencies of each case group were compared with the controls. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age and BMI, variants in luteinizing hormone/choriogonadotropin receptor (LHCGR) (rs13405728), C9orf3 (rs4385527) and insulin receptor gene (INSR) (rs2059807) were strongly associated with OA (Padjust < 0.01, <0.001 and <0.05, respectively); rs4385527 in C9orf3 was strongly associated with HA (Padjust< 0.001); variants in the thyroid adenoma associated gene (THADA) (rs13429458 and rs12478601), DENN/MADD domain containing 1A (DENND1A)(rs10818854), and C9orf3 (rs4385527) were significantly associated with PCOM (Padjust < 0.01, <0.001, <0.05 and <0.001, respectively). LIMITATIONS, REASONS FOR CAUTION The sample size of some case groups was relatively small, which therefore limited the statistical power of the analysis to a certain extent. WIDER IMPLICATIONS OF THE FINDINGS The present study indicates a potential common genetic basis of three PCOS clinical features. Other specific associated genes may play a synergistic role, leading to heterogeneous pathophysiological changes. Additionally, the increased frequency of PCOS-risk alleles in women with single PCOS clinical features suggests that these subjects have an elevated risk of developing the syndrome, although they cannot be currently diagnosed. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the National Basic Research Program of China (973 Program) (2012CB944700, 2011CB944502), the National Key Technology Research and Development Program(2011BAI17B00), the National Natural Science Foundation of China (81430029, 81201441, 81490743, 31371453), the Scientific Research Foundation of Shandong Province of Outstanding Young Scientist (2012BSE27089) and the Fundamental Research Funds of Shandong University(2014GN025). There were no competing interests. [ABSTRACT FROM PUBLISHER]

Background: Recurrent implantation failure (RIF) brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF. But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome.Methods/design: This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial (1:1 ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) or pre-implantation genetic testing for aneuploidy (PGT-A) will be enrolled and randomly assigned to two parallel groups. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant. The primary outcome is live birth rate.Discussion: The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800018783 . Registered on 9 October 2018. [ABSTRACT FROM AUTHOR]

Background: Women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with poor ovarian respond (POR) always have very low clinical pregnancy rates. In previous data, dehydroepiandrosterone (DHEA) was suggested as a promising treatment and maybe has a good pregnancy outcome. But there is no sufficient evidence from randomized clinical trials evaluating the effect of DHEA preconceptional treatment on live birth in POR.Methods: This trial is a multicenter active-placebo double-blind clinical trial (1:1 treatment ratio of active versus placebo). The infertile POR patients undergoing IVF or ICSI will be enrolled and randomly assigned to two parallel groups. Participants in these two groups will be given 4-12 weeks' treatment of DHEA or placebo, respectively. The primary outcome is live birth rate.Discussion: The results of this study will provide evidence for the effect of preconceptional DHEA treatment on IVF outcome in POR.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-15006909 . Registered on November 9, 2015. [ABSTRACT FROM AUTHOR]