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Introduction: Ovarian hyperstimulation syndrome (OHSS) is a severe complication associated with controlled ovarian stimulation (COS). GnRH agonist (GnRH-a) triggering is considered an efficient strategy to prevent OHSS in the high-risk patient. Methods: We performed a review of 11 cases of early and severe OHSS following GnRH-a triggering and freeze-all protocol. Electronic databases were searched from inception of each database until October 2021, to identify case reports and case series that reported OHSS after GnRH-a triggering and freeze-all approach describing patient demographics, COS protocol, and patient outcomes. Results: From the literature review, it is possible to suggest that (1) following GnRH-a triggering, the risk of early and severe OHSS is not totally cancelled; (2) despite it is not possible to predict the event, polycystic ovary syndrome is the most common risk factor; (3) the use of GnRH antagonist starting from the day of PU may represent a valid strategy for preventing OHSS in women with high-risk profile; (4) following the unexpected onset of OHSS, measuring serum levels of human chorionic gonadotropin (hCG) is helpful to exclude an inadvertent exogenous administration or a pregnancy. Conclusion: The statement that OHSS risk is eliminated when GnRH-a triggering, a freeze-all strategy, and no hCG in the luteal phase may generate the idea that this event cannot occur. Although rare, these cases have been observed in a relatively short period of time. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate whether or not maternal body mass index affects pregnancy rates following in vitro fertilization-intracytoplasmic sperm injection treatment. STUDY DESIGN: A total of 869 patients who had undergone in vitro fertilization-intracytoplasmic sperm injection treatment between 2012 and 2017 were included in this study. The participants were stratified according to maternal body mass index as Group 1 (body mass index <25 kg/m²; n=394), Group 2 (25 kg/m²< body mass index <30 kg/m²; n=303), and Group 3 (body mass index >30 kg/m²; n=172). RESULTS: While there were no differences between the groups in terms of age, smoking status, etiology of infertility, thyroid-stimulating hormone, prolactin levels, antral follicle count, and stimulation protocol (p>0.05), there was a significant statistical difference in terms of body mass index, duration of infertility, baseline follicle-stimulating hormone, luteinizing hormone, estradiol (E2), duration of stimulation, total gonadotropin dose required, peak E2 levels, progesterone levels, endometrial thickness on hCG administration, and cycle cancellation rate (p<0.05). In addition, the numbers of oocytes retrieved (groups 1 vs.. 3, p=0.011), metaphase II (groups 1 vs. 3, p=0.017) and 2 pronucleus (groups 1 vs. 3, p=0.010 and groups 2 vs. 3, p=0.010), and the rates of clinical pregnancy (40.1% vs. 33.2% vs. 23.8%, respectively), live births (33.6% vs. 23.7% vs. 13.9%, respectively), and miscarriages (17.7% vs. 28.6% vs. 44.7%, respectively) were also different between the groups (p<0.05). CONCLUSION: Our data suggest that there is an inverse impact of increased body mass index on laboratory and reproductive outcome parameters of in vitro fertilization-intracytoplasmic sperm injection treatment. Taking cost-effectiveness into consideration, weight loss should be suggested before ovulation is induced. [ABSTRACT FROM AUTHOR]

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Study questionWhat effect does maternal age have on the human oocyte's molecular response to in vitro oocyte maturation?Summary answerAlthough polyadenylated transcript abundance is similar between young and advanced maternal age (AMA) germinal vesicle (GV) oocytes, metaphase II (MII) oocytes exhibit a divergent transcriptome resulting from a differential response to in vitro oocyte maturation.What is known alreadyMicroarray studies considering maternal age or maturation stage have shown that either of these factors will affect oocyte polyadenylated transcript abundance in human oocytes. However, studies considering both human oocyte age and multiple stages simultaneously are limited to a single study that examined transcript levels for two genes by qPCR. Thus, polyadenylated RNA sequencing (RNA-Seq) could provide novel insight into age-associated aberrations in gene expression in GV and MII oocytes.Study design, size, durationThe effect of maternal age (longitudinal analysis) on polyadenylated transcript abundance at different stages was analyzed by examining single GV and single in vitro matured MII oocytes derived from five young (YNG; < 30 years; average age 26.8; range 20-29) and five advanced maternal age (AMA; ≥40 years; average age 41.6 years; range 40-43 years) patients. Thus, a total of 10 YNG (5 GV and 5 MII) and 10 AMA (5 GV and 5 MII) oocytes were individually processed for RNA-Seq analysis.Participants/materials, settings, methodsPatients undergoing infertility treatment at the Colorado Center for Reproductive Medicine (Lone Tree, CO, USA) underwent ovarian stimulation with FSH and received hCG for final follicular maturation prior to ultrasound guided oocyte retrieval. Unused GV oocytes obtained at retrieval were donated for transcriptome analysis. Single oocytes were stored (at -80°C in PicoPure RNA Extraction Buffer; Thermo Fisher Scientific, USA) immediately upon verification of immaturity or after undergoing in vitro oocyte maturation (24 h incubation), representing GV and MII samples, respectively. After isolating RNA and generating single oocyte RNA-Seq libraries (SMARTer Ultra Low Input RNA HV kit; Clontech, USA), Illumina sequencing (100 bp paired-end reads on HiSeq 2500) and bioinformatics analysis (CLC Genomics Workbench, DESeq2, weighted gene correlation network analysis (WGCNA), Ingenuity Pathway Analysis) were performed.Main results and the role of chanceA total of 12 770 genes were determined to be expressed in human oocytes (reads per kilobase per million mapped reads (RPKM) > 0.4 in at least three of five replicates for a minimum of one sample type). Differential gene expression analysis between YNG and AMA oocytes (within stage) identified 1 and 255 genes that significantly differed (adjusted P < 0.1 and log2 fold change >1) in polyadenylated transcript abundance for GV and MII oocytes, respectively. These genes included CDK1, NLRP5 and PRDX1, which have been reported to affect oocyte developmental potential. Despite the similarity in transcript abundance between GV oocytes irrespective of age, divergent expression patterns emerged during oocyte maturation. These age-specific differentially expressed genes were enriched (FDR < 0.05) for functions and pathways associated with mitochondria, cell cycle and cytoskeleton. Gene modules generated by WGCNA (based on gene expression) and patient traits related to oocyte quality (e.g. age and blastocyst development) were correlated (P < 0.05) and enriched (FDR < 0.05) for functions and pathways associated with oocyte maturation.Large scale dataRaw data from this study can be accessed through GSE95477.Limitations, reasons for cautionThe human oocytes used in the current study were obtained from patients with varying causes of infertility (e.g. decreased oocyte quality and oocyte quality-independent factors), possibly affecting oocyte gene expression. Oocytes in this study were retrieved at the GV stage following hCG administration and the MII oocytes were derived by IVM of patient oocytes. Although the approach has the benefit of identifying intrinsic differences between samples, it may not be completely representative of in vivo matured oocytes.Wider implications of the findingsTranscriptome profiles of YNG and AMA oocytes, particularly at the MII stage, suggest that aberrant transcript abundance may contribute to the age-associated decline in fertility.Study funding/competing interest(s)J.M.R. was supported by an Austin Eugene Lyons Fellowship awarded by the University of California, Davis. The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (awarded to P.J.R.; R01HD070044) and the Fertility Laboratories of Colorado partly supported the research presented in this manuscript.

PurposeUnlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC).MethodsThis is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used.ResultsSeven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P

PurposeThe purpose of the study was to determine whether diagnosis of endometriosis or endometriosis with endometrioma influences in vitro fertilization (IVF) outcomes in an ethnically diverse population.MethodsWomen undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31, 2009, at a university-affiliated infertility clinic, were retrospectively assessed for an endometriosis diagnosis. Differences in prevalence of endometriosis by ethnicity were determined, as well as differences in IVF success by ethnicity, with a focus on country of origin for Asian women. A multivariate model was generated to assess the relative contributions of country of origin and endometriosis to chance of clinical pregnancy with IVF.ResultsEndometriosis was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of endometrioma. Endometriosis prevalence in Asian women was significantly greater than in Caucasians (15.7 vs. 5.8%, p

Objectives: To determine the frequency of multiple gestations in Kohat City. Study Design: Retrospective longitudinal study. Place and Duration of Study: Labour Room and Neonatal Intensive Care Unit (NICU), Combined Military Hospital, Kohat Pakistan, from Jan 2019 to Dec 2020. Methodology: We included 5285 women delivered at Combined Military Hospital, Kohat Pakistan, during our study period.Basic data were collected from medical record files, and further information was gathered through telephonic interviews with the patients. The frequency of multiple gestations was calculated and compared with local and international statistics. Results: Out of 5285 deliveries during the study period, there were significant twin pregnancies 156(2.95%) and triplet pregnancies 11(0.21%). 167(3.16%) multiple deliveries were managed at our centre. Further probing showed that 109(65.3%) women used induction medication from registered medical practitioners or quakes/ spiritual healers to get pregnant. Conclusions: Multiple gestations and the use of induction therapy are much higher in Kohat compared to other parts of the country.

Abstract Background Anovulation is one of the common causes of infertility. Polycystic ovary syndrome (PCOS) is the most common disorder with chronic Anovulation. To the best of our knowledge, insulin resistance relates significantly to PCOS. Therefore administration of insulin-sensitizing drugs such as pioglitazone can be used for ovulation stimulation in PCO patients. Methods After obtaining approval from the Ethics Committee of Mashhad University of Medical Sciences, 61 patients with PCOS were enrolled in the study based on inclusion/ exclusion criteria. Patients were divided into two groups. The first group received 30 mg (mg) of pioglitazone daily from the second day of the menstrual period. The second one received a placebo. 150 mg clomiphene citrate was administered from the third to the seventh day of the menstrual cycle. Vaginal sonography was performed in all women, and in cases with the mature follicle, intrauterine insemination was conducted after human chorionic gonadotropin injection. Ovary stimulation and pregnancy rate were compared between groups. Results There were no differences between groups regard to demographic characteristics and infertility type. Body mass index was higher in the pioglitazone group (28.3 ± 3.8 versus 26.2 ± 3.5, P value = 0.047). The size of the follicle was not significantly different between groups (2.2 ± 1.4 versus 1.3 ± 1.1, P value = 0.742). pregnancy rate [4 (12.9%) versus 4 (13.3%), P value = 1] had no differences between groups. Conclusion Although the number of follicles was higher in the pioglitazone group, our study showed no differences in ovary stimulation and pregnancy rate.

Traditional biomarkers for predicting response to Controlled Ovarian Stimulation (COS) have limited capabilities, highlighted by the portion of patients who do not fit the response pattern predicted by their AMH levels and age. Identifying biomarkers that enable better forecasting of response to COS is desirable, potentially revealing patients at elevated risk of hyperstimulation and those who might produce a fewer than optimal number of oocytes. It has been proposed that alternative transcripts of the follicle-stimulating hormone receptor (FSHR) gene might contribute to variation in response to COS. We examined this hypothesis and produced the first comprehensive catalogue of FSHR transcript variants. Patterns of FSHR mRNA splice variants were analysed in 126 patients. RNA extracted from granulosa cells was subjected to long-read nanopore sequencing, enabling analysis of the entire FSHR transcript in a single continuous sequence 'read'.This was essential for determining whether variants affecting different parts of the transcript occur together or independently. Patients were categorised based on their COS response (high, low or normal), in addition to being classified by age, AMH level and the number of oocytes retrieved. Expression patterns of FSHR were compared to response to COS. Full-length FSHR transcript was detected in 97.6% of patients, and skipping Exon 6 was observed in 68%. In total, 9 distinct FSHR mRNA variants were detected. Five novel transcripts were identified involving partial insertion of ∼100bp segments of introns 1 or 2, seen in 6.6% of patients. Inconsistent responses to COS were identified in 53% and 33% of the patients predicted via their age or AMH levels, respectively. As expected, older age was associated with higher FSH requirement per oocyte collected (p=0.02), and AMH levels declined with age (p=0.01). AMH levels and amount of FSH injection per oocyte retrieved were negatively correlated (p<0.001). Interestingly, women ≥38 expressed novel variants more often than their younger counterparts (p=0.02), potentially indicative of an age-related decline in transcriptional fidelity in granulosa cells, which may have wider clinical relevance. The only transcript potentially linked to an altered response to COS was that lacking exon 6, which was associated with greater numbers of oocytes produced (p=0.009). This transcript was observed less often in older patients with low response to COS (p = 0.03). AMH and age-dependent response predictions were unreliable in many patients, highlighting the importance of discovering more powerful biomarkers. Our findings suggest that skipping Exon 6 may be associated with greater sensitivity to COS, indicating that FSHR mRNA profiling could potentially play a role in personalisation of stimulation protocols. This conclusion underscores the potential implications of research in this area for assisted reproductive technology. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is one of the most common reasons for infertility. The consensus of the treatment of infertile women with PCOS is ovulation induction (OI) for six to nine attempts before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Nowadays, more attention was paid to a rising, noninvasive treatment, intrauterine insemination (IUI), as some experts claimed IUI could benefit PCOS patients with infertility. Our study means to investigate the outcomes of IUI for PCOS patients and if patients' previous OI cycles can be a predictive factor for IUI outcomes. Methods: A total of 1,086 PCOS patients was included and 1,868 IUI cycles were performed between January 2007 and July 2021 in the department of assisted reproduction in Shanghai Ninth People's Hospital. All included patients underwent IUI treatments with letrozole+human menopausal gonadotropin (LE+hMG) for ovarian stimulation. Results: The pregnancy outcomes were not associated with the attempts of failed OI cycles previously. Specifically, the clinical pregnancy rate was 21.14% for PCOS patients without previous OI cycles, 21.95% for PCOS patients with 1-2 previous OI cycles and 23.64% for PCOS patients with 3 or more previous OI cycles (p=0.507). The corresponding live birth rate was 16.64%, 18.06%, and 18.68%, respectively, of which the difference was not statistically significant (p=0.627). The cumulative rate per patient was 38.59% for clinical pregnancy and 31.03% for live birth, and approximately 98% of the pregnancies occurred in the first 3 cycles of IUI. Conclusion: PCOS women with different attempts of OI cycles had similar pregnancy outcomes after IUI, thus a history of repeated failures of OI treatments was not a predictive factor for the pregnancy outcomes in IUI cycles. Most pregnancies occurred in the first three cycles of IUI, so we strongly recommended three attempts of IUI for PCOS women before they switched to IVF/ICSI. Generally, IUI might be an assist for infertile women with PCOS before IVF/ICSI and might accelerate pregnancy for target women without invasive manipulations. [ABSTRACT FROM AUTHOR]

Background: Hormone replacement therapy (HRT) regimen was suggested to be associated with a decreased rate of livebirth and a higher risk of hypertensive disorders of pregnancy (HDP) after frozen cleavage stage embryo transfer in women with polycystic ovary syndrome (PCOS). With the dramatically increased use of elective single embryo transfer, there is great need to explore the impacts of different endometrial preparation regimens on frozen single-blastocyst transfer in women with PCOS. Methods: In this study, a total of 3941 women who diagnosed with PCOS and underwent single-blastocyst transfer during their first cycles of frozen embryo transfer (FET) between March 2012 and December 2020 were included. We retrospectively compared the pregnancy and neonatal outcomes after frozen single-blastocyst transfer with endometrial preparation by HRT regimen (n = 3540), ovulation induction by human menopausal gonadotropin (hMG) regimen (n = 226), and ovulation induction by letrozole regimen (n = 175). Results: After adjustment for confounders withmultivariable logistic regression, the hMG regimen group [(58.4% vs. 49.6%; adjusted odds ratio (aOR): 1.43; 95% confidence interval (CI): 1.09-1.89)] and letrozole regimen group (58.9% vs. 49.6%; aOR: 1.42; 95% CI: 1.04-1.93) were associated with a higher rate of livebirth (primary outcome), compared with the group with HRT regimen. As to the secondary outcomes, the rate of pregnancy loss in the hMG regimen group (22.8% vs. 30.3%; aOR: 0.69; 95% CI: 0.48-1.00) and letrozole regimen group (16.9% vs. 30.3%; aOR: 0.48; 95% CI: 0.30-0.78) was also lower than that in the HRT regimen group. The pregnancy outcomes between the hMG regimen group and the letrozole regimen group were similar. We did not observe significant difference in the incidences of maternal and neonatal complications among these three groups. Conclusion: Ovulation induction regimen with letrozole or hMG for endometrial preparation was associated with a higher livebirth rate and a lower pregnancy loss rate in frozen single-blastocyst transfer cycles among women with PCOS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether children conceived using assisted reproductive technology (ART) or ovulation induction (OI) have greater cardiometabolic risk than children conceived without treatment.Design: Clinical assessments in 2018-2019 in the Upstate KIDS cohort.Setting: Clinical sites in New York.Patient(s): Three hundred thirty-three singletons and 226 twins from 448 families.Intervention(s): Mothers reported their use of fertility treatment and its specific type at baseline and approximately 4 months after delivery. High validity of the self-reported use of ART was previously confirmed. The children were followed up from infancy through 8-10 years of age. A subgroup was invited to participate in clinic visits.Main Outcome Measure(s): The measurements of blood pressure (BP), arterial stiffness using pulse wave velocity, anthropometric measures, and body fat using bioelectrical impedance analysis were performed (n = 559). The levels of plasma lipids, C-reactive protein, and hemoglobin A1c were measured using blood samples obtained from 263 children.Result(s): The average age of the children was 9.4 years at the time of the clinic visits Approximately 39% were conceived using fertility treatment (18% using ART and 21% using OI). Singletons conceived using fertility treatment (any type or using ART or OI specifically) did not statistically differ in systolic or diastolic BP, heart rate, or pulse wave velocity. Singletons conceived using OI were smaller than singletons conceived without treatment, but the average body mass index of the latter was higher (z-score: 0.41 [SD, 1.24]) than the national norms. Twins conceived using either treatment had lower BP than twins conceived without treatment. However, twins conceived using OI had significantly higher arterial stiffness (0.59; 95% CI, 0.03-1.15 m/s), which was attenuated after accounting for maternal BP (0.29; 95% CI, -0.03 to 0.46 m/s). Twins did not significantly differ in size or fat measures across the groups. The mode of conception was not associated with the levels of lipids, C-reactive protein, or glycosylated hemoglobin.Conclusion(s): Clinical measures at the age of 9 years did not indicate greater cardiometabolic risk in children conceived using ART or OI compared with that in children conceived without treatment.Clinical Trial Registration Number: ClinicalTrials.gov #NCT03106493. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the effects of laparoscopic cystectomy of endometriomas on intrauterine insemination with controlled ovarian hyperstimulation (COH + IUI) success in women with the disease. Material and methods: We performed a retrospective study with endometrioma patients having at least one patent fallopian tube. The study group consisted of 57 infertile patients with a history of laparoscopic cystectomy who underwent 83 COH + IUI cycles. The control group consisted of 88 patients with endometrioma who underwent 161 COH + IUI cycles without surgery. Results: The total number of antral follicles was significantly lower in the study group than in the control group (10.1 ± 5.1 vs 11.9 ± 5.0; p = 0.008). No significant difference was observed in the clinical pregnancy and live birth rates per cycle [(9.6% vs 7.6%; p=0.7175 OR: 1.195% CI: 0.6-2.1) and (7.2% vs 6.2%; p = 0.9544 OR: 1.1 95% CI: 0.5-2.1], respectively) between the operated and non-operated groups. Conclusions: The results of the study show that the presence of an endometrioma with at least one patent fallopian tube does not require any cystectomy before COH+IUI treatment because no improvement was observed in the treatment outcomes of the patients who underwent preceding surgery. We conclude that an operation may be taken into consideration when malignancy cannot be ruled out or severe pelvic pain related to endometrioma cannot be relieved. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this review is to define live birth rate (LBR) and clinical pregnancy rate (CPR) for women ≥ 40 undergoing ovulation induction (OI)/intrauterine insemination (IUI). Methods: A systematic review was performed in accordance with PRISMA guidelines using PubMed and Google Scholar. The primary and secondary outcomes of interest were LBR and CPR, respectively. Results: There were 636 studies screened of which 42 were included. In 8 studies which provided LBR for partner sperm, LBR/cycle ranged from 0 to 8.5% with majority being ≤ 4%. Cumulative LBR was 3.6 to 7.1% over 6 cycles with the majority of pregnancies in the first 4. In the four studies providing LBR for donor sperm cycles, LBR/cycle ranged from 3 to 7% with cumulative LBR of 12 to 24% over 6 cycles. The majority of pregnancies occurred in the first 6 cycles. There were three studies with LBR or CPR/cycle ≥ 1% for women ≥ 43. No studies provided data above this range for women ≥ 45. In 4 studies which compared OI/IUI and IVF, the LBR from IVF was 9.2 to 22% per cycle. In 7 studies which compared outcomes by stimulation protocol, no significant differences were seen. Conclusion: For women ≥ 40 using homologous sperm, the highest probability of live birth is via IVF. However, if IVF is not an option, OI/IUI may be considered for up to 4 cycles in those using partner sperm or 6 cycles with donor sperm. For women > 45, OI/IUI is likely futile but a limited trial may be considered for psychological benefit while encouraging consideration of donor oocyte IVF or adoption. Use of gonadotropins does not appear to be more effective than oral agents in this age group. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship between progesterone and oocyte maturity rate via estradiol to progesterone ratio (E/P) at the time of ovulatory trigger. Methods: This is a retrospective cohort study of first autologous IVF cycles from January to December 2018 from a private practice fertility center. Serum estradiol and progesterone levels were measured on the day of ovulatory trigger. E/P was calculated to control for degree of response. Embryos were cultured to the blastocyst stage for trophectoderm biopsy. Preimplantation genetic testing for aneuploidy (PGT-A) was performed using next-generation sequencing (NGS). Oocyte retrieval rate (oocytes retrieved/follicles ≥ 13 mm), maturity rate (MII/oocytes retrieved), and euploid rate (euploid/total biopsied embryos) were calculated. Clinical pregnancy, ongoing pregnancy (> 10 weeks), and live births following frozen embryo transfer (FET) were examined in relation to E/P. Regression analyses were performed to analyze E/P as a categorical value (defined by quartile) on oocyte maturity. Results: Two hundred eleven women underwent controlled ovarian hyperstimulation and had steroid levels at trigger available. Mean E at trigger was 3449 ± 2040 pg/mL while mean P was 1.13 ± 0.58 ng/mL, with mean E/P of 3.36 + 2.04. There were no differences between quartiles of E/P with respect to retrieval, maturity rate, or euploid rate. Two hundred eleven IVF cycles resulted in 138 euploid frozen embryo transfers. There were no differences between quartiles of E/P with respect to clinical pregnancy, ongoing pregnancy, or live birth rate. Conclusion: E/P ratio at the time of trigger does not impact oocyte retrieval rate, maturity rate, or euploid rate. Pregnancy and live birth outcomes were also not impacted. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of the descend range of estradiol (E2) at 48 h after oocyte retrieval compared with 24 h before oocyte retrieval on the pregnancy outcomes of fresh embryo transfer in the antagonist regimen. Methods: A retrospective study was done on the clinical data from 413 cycles of fresh embryo transfer, from January 2017 to March 2021. According to the descend range of E2 48 h after oocyte retrieval compared with 24 h before oocyte retrieval, they were divided into four groups according to the quartile method. Group A: The descend range is 0-25.0% of the overall descend range; Group B: 25.1%-50.0%; Group C: 50.1%- 75.0%; Group D: 75.1%-100.0%. The ovulation induction, embryological outcome and pregnancy outcomes were compared, and the relationship between E2 reduction and live birth rates was analyzed by logistic regression. Results ：There were significant differences in the total amount of Gn, days of antagonist use, live birth rates, implantation rates and clinical pregnancy rates among the four groups (all P＜0.05). The live birth rate of group A was higher than group D, group B was higher than those of group C and group D, and the implantation rates of group A and group B were higher than group D (all P＜0.008 3). After adjusting for the factors of differences among groups, the live birth rates of groups A and B were significantly higher than those of group D (OR=2.079, 95%CI: 1.138-3.799, P=0.017; OR=2.187, 95%CI: 1.213-3.944, P=0.009). Conclusions: In the antagonist regimen, the live birth rate of fresh embryo transfer in patients with a greater descend range of E2 at 48 h after oocyte retrieval is lower than that in patients with less descend range of E2. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome is a common complication in assisted reproductive technology. It usually occurs after two weeks or more of induced ovulation. However, the spontaneous ovarian hyperstimulation syndrome (sOHSS) is extremely rare. Some clinical cases showed that the etiology of sOHSS was related to the mutations of follicle stimulating hormone receptor gene, the high level of human chorionic gonadotropin (hCG), the high level of thyroid-stimulating hormone (TSH), and gonadotropin pituitary adenoma. In this paper, we report a case of twin pregnancy complicated with sOHSS, and further study the possible etiology, diagnosis and treatment of sOHSS. [ABSTRACT FROM AUTHOR]

Study Question: Are children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions?Summary Answer: Infertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy.What Is Known Already: Asthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments.Study Design, Size, Duration: Upstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up.Participants/materials, Setting, Methods: Women reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure.Main Results and the Role Of Chance: Compared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI).Limitations, Reasons For Caution: Childhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association.Wider Implications Of the Findings: Though future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age.Study Funding/competing Interest(s): This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Different types of drugs are used for the stimulation of ovulation. These drugs include "Folliclestimulating (FSH) drugs” and “Modulating-ovulation drugs. Objectives: The present study was aimed to assess the association of visual disturbances that might occur in infertile women who receive different types of ovarian induction drugs. Materials and Methods: This study included a total of 300 patients with primary infertility due to anovulation, aged 20 - 40 years, recruited from the Obstetrics and Gynecology Outpatient Clinic, Menoufia University Hospital. This study was conducted between January 2019 to June 2020. The participants were categorized into three groups (100 each) based on the use of one of three different drugs, namely, Gonal F, Clomid, and HMG groups, The number of follicles, results of pregnancy tests, and ocular clinical condition were assessed. Results: The study showed that the average number of follicles per cycle was significantly lower in the Clomid group, and the visual disturbances were met in 3% of the participants in the Clomid group. Conclusion: It could be concluded that clomid might be associated with visual disturbance. It is recommended that gynaecologists advise women receiving different types of ovarian induction drugs to closely visit an ophthalmologist before suggesting these drugs to assess their risk of developing visual disturbances. [ABSTRACT FROM AUTHOR]

Background: Infertility remains a significant public health concern. An issue with controlled ovarian stimulation (COS) is the selection of an exogenous gonadotropin (Gn) regimen, which is mainly based on urinary follicle-stimulating hormone (uFSH), recombinant follicle-stimulating hormone alfa (rFSH-alfa), and human menopausal gonadotropin (HMG). In addition, most previous studies focused on the clinical pregnancy rates or live birth rates (LBR) per transfer cycle, but not on the cumulative live birth rate (CLBR) per started cycle. The CLBR, appears to be a more comprehensive and accurate universal measure of IVF treatment success. Therefore, this study aimed to compare the cumulative live birth rate (CLBR) between rFSH-alfa and uFSH regimens for ovarian stimulation. Methods: This retrospective cohort study included patients who underwent assisted reproductive technology (ART) with gonadotropin-releasing hormone (GnRH) agonist long protocol between March 2009 and December 2018. Patients were grouped according to the Gn regimen received (rFSH-alfa or uFSH). The main outcome was CLBR, which defined as the first live birth following the use of all fresh and frozen embryos derived from a single COS cycle. Results: A total of 1078 cycles were analyzed (314 with rFSH-alfa and 764 with uFSH). The rFSH-alfa group was characterized by a higher number of retrieved oocytes (13.3 vs. 11.0) and transferable embryos (5.0 vs. 4.0), a higher fresh embryo transfer rate (35.0% vs. 26.3%), and a higher multiple birth rate among the fresh embryo transfer cycles (8.2% vs. 2.5%) (P < 0.05). There were no differences in pregnancy rate (32.7% vs. 33.8%) and LBR (25.5% vs. 26.9%) per transfer cycle (P > 0.05). No significant difference was found in clinical outcomes among the frozen embryo transfer cycles (P > 0.05). The CLBR per started cycle in the rFSH-alfa group was higher than in the uFSH group (53.5% vs. 43.1%, P < 0.05). After adjustment, rFSH-alfa was independently associated with a higher CLBR (OR = 1.56; 95%CI = 1.18–2.05; P = 0.0018). Conclusions: rFSH-alfa and uFSH have similar pregnancy rates and LBR per transfer cycle, rFSH-alfa might achieve more transferrable blastocysts and higher CLBR per started cycle compared to uFSH. [ABSTRACT FROM AUTHOR]

In this study, 19 mares brought to the clinic at different times with the complaint of not getting pregnant were followed up. For this purpose, changes in the uterine and ovarian dynamics of mares and behavioral changes in estrus were followed and evaluated. In particular, it was attempted to increase the chance and rate of pregnancy by providing ovulation with ovulation follow-up followed by a single dose of hCG administration (Chorulon, 3.000 IU). All manipulations and applications in the study were carried out between March and July, that is, during the breeding season of the mares. During the study, a B-mode real-time ultrasonography device was used for ovary and uterus examinations of the mares. For the insemination of the mares, fresh semen was obtained from breeding stallions by the artificial vagina method and analyzed fresh semen was used. The intracornual insemination method was used as an artificial insemination method. Pregnancy controls were performed twice on the 15th and 30th days after insemination and the pregnancy status was evaluated according to the criteria of the presence of an embryonic sac in cornu uteri. While the average follicle diameter was around 43.7 millimeter (mm) at the stage when estrus symptoms were at their peak, the diameter of the follicle was 36.2 mm in the USG controls performed at the beginning of estrus. Uterine oedema was measured as 1.78 in the initial phase of estrus, 3.84 in the most intense phase of estrus, and 2.36 during insemination during the same periods. The pregnancy rate was found to be 68% (13/19). As a result, it is recommended to administer gonadotropic hormones such as hCG at an appropriate dose (3000 IU) to mares who have trouble conceiving, especially in cases of delayed ovulation. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Ovulation induction is the first choice of treatment for PCOS patients with fertility requirements. According to the current domestic and international treatment guidelines, clomiphene citrate (CC) is the traditional first-line drug to induce ovulation for infertile women with PCOS. However, the response of CC ovulation treatment varies significantly for different patients. It was reported that about 40% of PCOS patients cannot respond to CC, that is, CC resistance. This paper provides a review on the research progress of predictive indicators for PCOS infertile women with CC resistance as well as alternative ovulation induction strategies in recent years. This paper mainly expounds the predictive indicators for PCOS patients with CC resistance from the perspective of phenotype, biochemical characteristics and genetics. Single or combined schemes are selected in the treatment methods of letrozole (LE), gonadotropin (Gn), laparoscopic ovarian perforation (LOD), in vitro fertilization (IVF) and adjunctive therapy of traditional Chinese medicine to elaborate their alternative ovulation induction strategies, and the advantages and potential shortcomings of these single and combined schemes are discussed to provide more accurate and individualized ovulation induction schemes for PCOS infertile women. [ABSTRACT FROM AUTHOR]

We aimed to investigating the effects of metformin (MET) in combination with alpha lipoic acid (ALA) on hormonal and biochemical parameters, in polycystic ovary syndrome (PCOS) women undergoing intracytoplasmic sperm injection (ICSI). This experimental pilot study with a randomized design was carried out on 40 PCOS women in two groups: (1) MET group, administered 1,500 mg/day MET, and (2) MET (1,500 mg/day)+ALA (1,800 mg/day) group. Drugs were administered from the third day of the previous cycle until the day of oocyte aspiration (six weeks of treatment in total). MET+ALA significantly increased the number of maturated oocytes and the rate of fertilization when compared to the MET group. Combination MET+ALA could increase significantly the number of oocytes retrieval and the number of good-quality embryos. Also, the malondialdehyde (MDA) level decreased significantly in the MET+ALA group and the total antioxidant capacity (TAC) level increased significantly in the MET+ALA group compared to the MET group. Also, fasting blood sugar (FBS), insulin, luteinizing hormone (LH), and LH/follicle stimulating hormone (FSH) levels were significantly lower in the MET+ALA group. The pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, clinical pregnancy, miscarriage, and live births between the control and study groups. The combination of MET+ALA treatment could moderate the complications of PCOS and subsequently improve oocyte and embryo quality. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the impact of hyperandrogenism (HA) on the outcomes of ovulation induction (OI) using gonadotropin and intrauterine insemination (IUI) in patients with polycystic ovary syndrome (PCOS). Methods: This was a retrospective cohort study including 415 patients undergoing OI using gonadotropin and IUI treatment between January 2018 and December 2020 at a single infertility center. Baseline characteristics, clinical and laboratory parameters, and pregnancy outcomes were investigated. Results: Among the study population, there were 105 hyperandrogenic (25.3%) and 310 non-hyperandrogenic patients (74.7%). The live birth rate was lower in the HA group than in the non-HA group, but this difference did not reach statistical significance due to the limited sample size (14.3% vs. 21.0%, relative risk=0.68; 95% CI, 0.41–1.14, p=0.153). No predictive factors for live birth were identified through logistic regression analysis. Conclusion: HA did not negatively affect the outcomes of OI using gonadotropin and IUI cycles in Vietnamese women with PCOS. The result may not be applicable elsewhere due to the large variation in the characteristics of women with PCOS across races and populations. [ABSTRACT FROM AUTHOR]

Abstract Background Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations. Results Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P

Abstract Background Contrary to overt hypothyroidism, the true impact of subclinical hypothyroidism on fertility has not been well established. This study aimed to investigate whether serum thyroid stimulating hormone (TSH) values between 2.5 and 4.5 mIU/L are associated with lower pregnancy rates compared to TSH levels between 0.3 and 2.5 mIU/L in women undergoing ovulation induction with gonadotropins and intrauterine insemination (IUI) for unexplained infertility. Methods Medical records of couples with unexplained infertility who underwent IUI treatment between January 2013 and December 2018 were reviewed retrospectively. Cycle characteristics and pregnancy outcomes of patients with serum TSH levels between 0.3–2.5 mIU/L and 2.5–4.5 mIU/L were compared. Primary outcome measures were clinical pregnancy and live birth rate. Secondary outcome measures were total dose of gonadotropin administration, duration of ovulation induction and miscarriage rate. Results A total of 726 euthyroid women who underwent 1465 cycles of ovulation induction with gonadotropins and IUI were included in the analyses. Patient and cycle characteristics of the two study groups were similar. No statistically significant differences could be detected in the clinical pregnancy (p = 0.74) and live birth rates (p = 0.38) between the two groups. Duration of ovulation induction, total gonadotropin dosage, number of follicles > 17 mm on the trigger day and the miscarriage rates were similar in the two groups. Conclusion In euthyroid women undergoing ovulation induction with gonadotropins and IUI for unexplained infertility, the range of preconceptional serum TSH values between 2.5 and 4.5 mIU/L is not associated with lower pregnancy rates when compared to TSH levels between 0.3 and 2.5 mIU/L.

Purpose of investigation: Current infertility treatment strategies may result in ovarian hyperstimulation syndrome (OHSS), which can present with hemodynamic instability that involves hemoconcentration, hypoxia, and liver and renal dysfunction that may result from thrombosis. This study’s purpose was to measure the serum biochemical oxidative stress markers in women with severe OHSS. Material and methods: For this prospective controlled study, serum levels of ischemia modified albumin (IMA), total antioxidant capacity (TAC), total oxidative capacity (TOS), oxidative stress capacity (OSI), and serum malondialdehyde (MDA) were measured in women with (n = 25) and without (n = 27) OHSS. Results: In our study, we observed significant differences between the two groups in terms of IMA, TAC, TOS, OSI, and MDA levels. High oxidative stress parameter levels in the OHSS group may indicate that OHSS is an oxidative stress condition. A bivariate correlation analysis revealed a significant correlation between serum TOS level, OSI ratio, and embryo or oocyte quality scores. In addition, there was a negative, non-significant tendency among OHSS patients regarding high IMA, OSI, TOS, and MDA levels and low oocyte and embryo scores. Pregnancy results were not affected in a statistically significantly manner. Conclusion: These results might indicate that oxidative stress status and oxygen radicals may negatively affect ART cycle outcomes.

Importance: Understanding the potential risks associated with fertility treatments (FTs) can guide clinical decision and patient counseling., Objective: To investigate the validity of the association between the development of female-specific malignancies including ovarian, endometrial, breast, and cervical cancer after FT., Data Sources: A search of systematic reviews and meta-analyses was performed from inception to April 2022 within several databases: Cochrane Database of Systematic Reviews, EMBASE, Google Scholar, and PubMed., Study Selection and Synthesis: The inclusion criteria required the incidence of each cancer subgroup to be stated in both the defined treatment group (controlled ovarian stimulation and/or in vitro fertilization [IVF] or intracytoplasmic sperm injection) and the control group (no-FT, general population). From 3,129 identified publications, 11 meta-analytical reviews consisting of 188 studies were selected for synthesis., Main Outcome: The primary outcome of interest was incidence of each subgroup of cancer in the "FT" group compared with the "no-FT" group., Results: A statistically significant increase in incidence of ovarian (1,229/430,611 in FT group vs. 27,358/4,263,300 in no-FT group) cancer (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.00-1.45) and borderline ovarian tumors (117/414,729 in FT group vs. 934/2,626,324 in no-FT group) (OR, 1.87; 95% CI, 1.18-2.97) was observed. The incidence of ovarian cancer was higher with FT and IVF specifically (OR, 1.65; 95% CI, 1.07-2.54). For borderline ovarian tumors, the incidence was higher, not only with FT overall and IVF, but also according to the fertility drug regimen applied: clomiphene citrate (CC) only (OR, 1.99; 95% CI, 1.02-3.87), human menopausal gonadotropin only (OR, 3.46; 95% CI, 1.39-8.59), and CC and human menopausal gonadotropin combined (OR, 3.79; 95% CI, 1.47-9.77). When using the threshold for statistical significance, the meta-analyses relevant to ovarian cancers remained statistically significant (random-effects method). However, none of the examined associations could claim either strong or highly suggestive evidence., Conclusion and Relevance: An observed association between ovarian cancer (including borderline ovarian tumors) and FT has been demonstrated. The association between FT and female-specific malignancy remains a contentious topic because there have been contradictory outcomes among meta-analyses. This umbrella review interrogates existing systematic reviews and meta-analyses on this topic and concludes that a statistically significant increase in the incidence of ovarian cancer and borderline ovarian tumors is associated with FT. These findings have a significant clinical impact because it helps to inform and provide effective counseling for patients undergoing FT., Competing Interests: Declaration of Interests S.S. has nothing to disclose. J.F.B. has nothing to disclose. L.S.K. has nothing to disclose. N. Galazis has nothing to disclose. B.N.D. has nothing to disclose. K.J.G. has nothing to disclose. T.B.-M. has nothing to disclose. B.P.J. has nothing to disclose. N. Getreu has nothing to disclose. M.C. has nothing to disclose. A.M. has nothing to disclose. M.A.-M. has nothing to disclose. J.B.-N. has nothing to disclose. J.R.S. has nothing to disclose. J.Y. has nothing to disclose. D.T. has nothing to disclose. T.B. has nothing to disclose. S.G.-M. has nothing to disclose. J.Y.V. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Anovulation is very common and has several different clinical manifestations, including amenorrhea, oligomenorrhea and abnormal uterine bleeding. Various mechanisms can cause anovulation. The clinical consequences and commonest chronic anovulatory disorder, polycystic ovary syndrome (PCOS), has a prevalence that ranges between 6 to 10% of the global population. While multiple causes can eventually result in PCOS, various methods have been described in the literature for its management, often without ascertaining the underlying cause. Ovulation Induction (OI) is a group of techniques that is used in women with PCOS who are looking to conceive and are unbale to do so with natural means. This narrative review presents a summary of the current evidence and available techniques for OI in women with PCOS, highlighting their performance and applicability.

ObjectiveTo describe a clinical approach to and outcomes of IVF in reproductive-aged cancer survivors receiving targeted cancer therapies.DesignCase report.SettingNot applicable.Patient(s)The first case is of a female patient with metastatic lung cancer receiving long-term crizotinib, an anaplastic lymphoma kinase inhibitor. The second case is of a female patient with metastatic colon cancer receiving long-term denosumab, a RANKL antibody. Both patients presented desiring fertility.Intervention(s)In vitro fertilization.Main outcome measure(s)Live birth and embryo banking.Result(s)The potential impact of targeted therapy on oocytes and pregnancy was investigated via literature review and pharmaceutical company inquiries. After oncologic, fertility, and psychological counseling, both survivors underwent ovarian stimulation, IVF, and preimplantation genetic screening. One couple achieved live births of dizygotic twins via gestational surrogacy. The second couple froze one euploid blastocyst for future fertility. Both survivors are stable from their cancer standpoints.Conclusion(s)Successful fertility treatments are possible in the context of exposure to crizotinib and denosumab.

PURPOSE: The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, good prognosis patients predominantly with secondary infertility who are less than 35 years of age. METHODS: Using de-identified clinic records, 414 women

Objective: To explore the best timing for frozen embryo transfer (FET) after ovarian stimulation and egg retrieval using the clomiphene citrate (CC) + human menopausal gonadotropin (hMG) ovulation induction regimen through a retrospective analysis. Methods: Data of patients who underwent CC + hMG ovulation induction and FET from January 2014 to December 2019 were analyzed retrospectively. The patients were divided into three groups according to the interval from egg retrieval to FET: CC1 (within 1 menstrual cycle), CC2 (2 menstrual cycles), and CC3 (≥ 3 menstrual cycles). Indicators such as hormone levels and pregnancy outcomes were recorded to explore the effect of different intervals on pregnancy outcome. Results: A total of 1,082 transfer cycles were included in this retrospective analysis. The implantation, clinical pregnancy, and live birth rates in the CC1 group were significantly lower than those in the CC2 and CC3 groups (P < 0.05). The E2/P4 ratio on progesterone injection day (3 days before thawed embryo transfer) was lower in the CC1 group than in the other groups (P < 0.05). After adjusting for all factors using multifactor regression analysis, the interval between egg retrieval and FET was found to be an independent predictor of the implantation, pregnancy, and live birth rates. Conclusion: An interval of more than one menstrual cycle between the day of egg retrieval after ovarian stimulation with the CC + hMG ovulation induction regimen and the day of FET can result in high implantation, clinical pregnancy, and live birth rates, which can lead to an improved pregnancy outcome.

What is the influence of ethnicity on the outcome of ovulation induction with clomifene citrate in women with polycystic ovary syndrome (PCOS)? This was a retrospective cohort study. In total, 420 women diagnosed with PCOS who were of Northern European, Mediterranean, African, South-East Asian or South American descent, and who started ovulation induction treatment with clomifene citrate, were included. All women were treated with clomifene citrate according to a standardized treatment regimen. The minimal effective dose of clomifene citrate and prevalence of clomifene resistance (CRA) were assessed, and the chance of becoming ovulatory was predicted. Differences were observed in body mass index (P = 0.008), waist circumference (P = 0.036) and serum LH, insulin and androgen concentrations (all P < 0.001) in women of different ethnicities with PCOS. Compared with women of Northern European descent, the minimal effective dose of clomifene citrate in women of other ethnic groups was not significantly different. The prevalence of CRA (P = 0.574) was similar in all ethnic groups A similar chance of ovulation (P = 0.504) was predicted for the different ethnic groups. This is the first study aiming to link ethnicity to ovulation induction outcome in PCOS. Although women of different ethnicities who have PCOS exhibit a variation in phenotypic expression, there do not appear to be differences in the prevalence of clomifene-resistant anovulation or the minimal effective dose of clomifene citrate. Furthermore, a prediction model revealed no significant differences in the predicted chance of ovulation. A larger cohort is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background and Objectives: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women frequently presenting with anovulatory infertility. Low successful pregnancy and live birth rates even after successful ovulation induction (OI) and in vitro fertilization (IVF) in these patients indicate that endometrial dysfunction may be another important factor contributing to infertility. Vitamin D acting through nuclear receptors induces the expression of various genes required for cell growth and differentiation and plays a crucial role in reproduction. Homeobox 10 (HOXA10) may be one of the potential targets for vitamin D action. HOXA10 gene product promotes the differentiation of endometrial cells, making the endometrium receptive for implantation. The present study was undertaken to determine the effect of circulating vitamin D levels on HOXA10 gene expression in endometrial tissues and its possible influence on the reproductive outcome of PCOS patients undergoing OI procedure. Materials and Methods: A prospective cohort study was conducted on 110 infertile PCOS patients. The patients were divided into two groups: Group 1: Vitamin D ≥20 ng/ml, Group 2: Vitamin D <20 ng/ml. Endometrial samples were obtained from 22 patients using pipelle biopsy, used to determine HOXA10 mRNA (messenger ribonucleic acid) expression by quantitative RT-PCR (reverse transcription-polymerase chain reaction) and protein expression by Western blotting. OI was performed using Clomiphene citrate or Letrozole from the 3rd day of the cycle, and patients were followed up for a maximum of five cycles. Attainment of successful pregnancy was considered a positive outcome.Results: Both the groups were similar in mean age and other endocrine parameters. Serum vitamin D levels were significantly low (P < 0.001), and BMI (body mass index) was significantly high (P = 0.032) in group 2 compared to group 1. Endometrial HOXA10 mRNA (by quantitative rtPCR) and protein expression (by western blotting) were significantly low in group 2 compared to group 1. The clinical pregnancy rate was low in group 2 (28.6%) compared to group 1 (42.3%), but this difference was not significant (P = 0.22). On regression analysis adjusted for age and BMI, vitamin D was an independent predictor of successful pregnancy after OI (P = 0.09). Conclusion: Circulating vitamin D levels influence the endometrial HOXA10 gene expression, and this may be reflected on the reproductive outcome of infertile PCOS patients undergoing OI. [ABSTRACT FROM AUTHOR]