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Background: Few previous studies have addressed the impact of COVID-19 infection status on assisted reproductive technology outcomes. The purpose of this study was to assess whether COVID-19 infection affects ovulation induction outcomes and the laboratory outcomes of women undergoing assisted reproductive technology treatment. Methods: In total, 363 patients were divided into three groups: the COVID-19 infection group (group A, n = 49), the COVID-19 recovery group (group B, n = 119) and the COVID-19 non-infection group (group C, n = 195). Intergroup comparisons of baseline characteristics, stimulation characteristics and laboratory outcomes were performed. Results: The Gn dosage in group A was significantly higher than those in groups B and C. The duration of Gn treatment was longer in group A than in group B. In group B, the number of high-quality blastocysts was lower than that in group C. The rates of blastocyst formation (42.56%) and high-quality blastocyst formation (12.05%) in group B were significantly lower than those in group A (51.51%; P = 0.003, 16.58%; P = 0.026) and C (48.20%; P = 0.005, 16.49%; P = 0.002). The high-quality blastocyst rate in group C (34.20%) was the highest and was different from that in group B (28.33%). The main risk factor for high-quality blastocyst formation according to multivariate logistic regression analysis was recovery from COVID-19 (0.599, 95% CI: 0.360–0.996; P = 0.048). Conclusion: Asymptomatic or mild COVID-19 infection prior to oocyte retrieval may not has a significant negative effect on ovulation induction outcomes or laboratory outcomes, although the number of Gn days and dose of Gn may increase. In addition, we should pay attention to infertile women recovering from COVID-19 infection and be aware of the significant reduction in the number of high-quality blastocysts in this population. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. While pregnancy and hormonal stress can trigger SLE flare-ups, the effects of assisted reproductive therapies (ARTs) on SLE patients are not well defined. We conducted a search of PubMed/Medline, Embase, and CENTRAL until March 20, 2024, to find observational studies assessing the prevalence of SLE flares and pregnancy outcomes following ARTs. Our analysis included random-effects meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for evaluating evidence quality. Five studies involving 237 SLE women who underwent ARTs were eligible. The meta-analysis indicated a prevalence of SLE flares at 17% (95% CI: 10–25%) with moderate-quality evidence. The pooled prevalence of arthritis flares was 7% (95% CI: 0–25%) with low-quality evidence. Successful pregnancy rates were 58% (95% CI: 43–72%), and live birth rates were 96% (95% CI: 83–100%), both with low-quality evidence. Moderate-quality evidence showed pregnancy complications, including preterm premature rupture of membranes (PPROM) at 8% (95% CI: 3–16%), miscarriages at 2% (95% CI: 0–9%), intrauterine fetal demise (IUFD) at 4% (95% CI: 0–11%), and preeclampsia at 7% (95% CI: 1–17%). Low-quality evidence showed preterm labor at 10% (95% CI: 0–32%) and ovarian hyperstimulation syndrome (OHSS) at 2% (95% CI: 0–11%). SLE flares, as well as pregnancy complications such as IUFD, miscarriage, PPROM, and preeclampsia in ART recipients, are equivalent to those in spontaneous conception. This indicates that ART is relatively safe for SLE patients with meticulous pregnancy planning. Key Points • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. • Pregnancy in women with SLE poses elevated maternal and fetal risks compared to healthy women. • SLE flares and pregnancy complications while receiving ART are equivalent to those in spontaneous conception and ART is relatively safe for SLE patients. [ABSTRACT FROM AUTHOR]

Introduction: The question of whether assisted reproductive technologies (ART) and ovulation induction are related to a higher incidence of ovarian tumors (OTs) is still controversial in the literature. Methods: We performed a comprehensive search of PubMed, Embase, and Web of Science databases for case–control and cohort studies that investigated ART and ovulation induction exposure as risk factors for OT in infertile women. Odds ratios (OR) with 95% confidence intervals (CI) were employed for all endpoints. Results: A total of nine case–control and twelve cohort studies were included, encompassing 439,477 women. ART was not associated with a higher risk of OTs (OR 1.05; 95% CI 0.86–1.29; p = 0.64; I2 = 36%), nor when considering only borderline OTs (OR 1.13; 95% CI 0.84–1.51; p = 0.42; I2 = 31%). In a subgroup analysis by study type, the risk difference of OTs remained non-significant for case–control (OR 1.12; 95% CI 0.70–1.78; p = 0.65; I2 = 60%) and cohort studies (OR 1.05; 95% CI 0.87–1.27; p = 0.60; I2 = 1%). For borderline OTs, the difference between groups was also non-significant for case–control studies (OR 1.44; 95% CI 0.73–2.87; p = 0.30; I2 = 40%) and cohort studies (OR 1.00; 95% CI 0.75–1.34; p = 0.99; I2 = 24%). Conclusion: In this systematic review and meta-analysis, ART exposure in infertile women was not associated with a higher risk of OTs in general or borderline tumors, even when accounting for study type differences. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5 mg letrozole and 50 mg Clomiphene Citrate (CC) daily or 2.5 mg letrozole alone from 2nd to 6thday of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial Registration The trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020. [ABSTRACT FROM AUTHOR]

Background: Ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) remains challenging, and several biomarkers have been evaluated for their ability to predict ovulation. The predictive ability of candidate biomarkers, particularly with letrozole-based therapy in infertile PCOS women, remains inconclusive as it is yet to be evaluated in a prospective study. Aim: To assess the role of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH)/FSH ratio, testosterone and free androgen index (FAI) as predictors of ovarian response to letrozole-based OI therapy during OI cycles in infertile women with PCOS from North India. Settings and Design: A prospective cohort study was conducted in a tertiary care hospital in north India. Materials and Methods: The study enrolled 80 infertile women with PCOS, diagnosed according to the Rotterdam criteria. OI was conducted using letrozole with or without human menopausal gonadotropin. Baseline endocrine and metabolic parameters, including serum AMH, FSH, LH, testosterone and FAI levels, were measured using ELISA or chemiluminescence methods on day 2 of the menstrual cycle. Follicular response to OI was monitored by transvaginal ultrasonography. Statistical Analysis Used: Descriptive and inferential statistical analyses were conducted, including Mann–Whitney, Kruskal–Wallis, Independent t-test, analysis of variance, Fisher’s exact test and receiver operating characteristic curve analysis. Data were processed using Microsoft Excel and analysed with SPSS software, version 25.0. P < 0.05 was considered statistically significant. Results: Of 80 women enrolled, 74 responded to letrozole-based OI, while six were non-responders. Body mass index (BMI), serum testosterone and pre-treatment AMH levels significantly correlated with follicular response, with higher values linked to reduced responsiveness. The likelihood ratio+ (95% confidence interval) was 3.32 (2.45–5.06) for AMH, 1.97 (1.03–3.78) for BMI and 1.93 (1.22–3.08) for testosterone. The odds ratio for AMH was 2.88 (1.01–8.21) and 1.25 (1.02–1.53) for BMI. An AMH cut-off of ≤16.43 ng/mL predicted ovarian response with an AUC of 0.88. Conclusions: Pre-treatment AMH levels, along with BMI and serum testosterone, are significant predictors of ovarian response to letrozole-based OI in infertile women with PCOS.

Understanding the potential risks associated with fertility treatments (FTs) can guide clinical decision and patient counseling. To investigate the validity of the association between the development of female-specific malignancies including ovarian, endometrial, breast, and cervical cancer after FT. 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. 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. The primary outcome of interest was incidence of each subgroup of cancer in the "FT" group compared with the "no-FT" group. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract Background Theoretically, endocrine fluctuations occurring during infertility treatments, including ovulation induction (OI) and assisted reproductive techniques (ART), could be associated with an increased risk of benign breast diseases (BBDs). To date, no studies have been conducted on this association. Therefore, the present study investigated the association between different types of infertility treatments and BBDs. Methods This case‒control study was conducted in Arash Women’s Hospital, Tehran, Iran. The case group included infertile women diagnosed with BBDs without atypia, and the control group included infertile women without breast disease. Breast imaging studies (mammography/ultrasound) were performed for BBD screening, and the diagnosis was confirmed by histopathological examination. Study variables were collected retrospectively from medical records, hospital databases, and questionnaires. Results Finally, 154 infertile women, including 50 cases (BBDs) and 104 controls (no BBDs), were compared. Our data showed that 66% of cases and 61.4% of controls had undergone at least one course of infertility treatment. There was no association between BBD risk and previous infertility treatments (OR = 1.21; 95% CI = 0.59–2.46), ART (OR = 1.14; 95% CI = 0.90–1.44), or OI cycles (OR = 1.13; 95% CI = 0.98–1.32). Stratification by confounding variables did not change these results. Conclusions It seems that there is no association between BBDs in infertile women and the type, duration, or number of prior infertility treatments; however, considering the small sample size of the study, the clinical significance of this finding should not be neglected. Therefore, we consider it essential to carry out more extensive, detailed, and prospective studies to distinguish the association of BBDs with different infertility treatments and medications.

Abstract Background Polycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS. Methods Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups. Results Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p

Hyperreactio luteinalis (HL) and ovarian hyperstimulation syndrome during pregnancy are both benign conditions where the ovaries are enlarged with presence of multiple thin-walled cysts. The differential diagnosis is ovarian malignancy. Hyperandrogenism with resultant maternal virilisation could be seen in some cases of HL as well as in androgen secreting tumours. We report a 41-year-old female patient who underwent ovulation induction due to secondary infertility at a high-risk pregnancy unit in Muscat, Oman, in 2022. She had recurrent hospital admission with abdominal pain and large multicystic enlargement of both ovaries. She developed virilisation features by 35 weeks of pregnancy. Lower segment caesarean section was done at 36 weeks gestation for breech presentation with intra-uterine growth restriction. Magnetic resonance imaging confirmed the benign nature of the cysts. Ovarian cysts and hyperandrogenism gradually resolved 3-months post-delivery. Awareness, judicious imaging and close monitoring in such cases can result in live birth and avoid oophorectomies. [ABSTRACT FROM AUTHOR]

Background: Theoretically, endocrine fluctuations occurring during infertility treatments, including ovulation induction (OI) and assisted reproductive techniques (ART), could be associated with an increased risk of benign breast diseases (BBDs). To date, no studies have been conducted on this association. Therefore, the present study investigated the association between different types of infertility treatments and BBDs. Methods: This case‒control study was conducted in Arash Women's Hospital, Tehran, Iran. The case group included infertile women diagnosed with BBDs without atypia, and the control group included infertile women without breast disease. Breast imaging studies (mammography/ultrasound) were performed for BBD screening, and the diagnosis was confirmed by histopathological examination. Study variables were collected retrospectively from medical records, hospital databases, and questionnaires. Results: Finally, 154 infertile women, including 50 cases (BBDs) and 104 controls (no BBDs), were compared. Our data showed that 66% of cases and 61.4% of controls had undergone at least one course of infertility treatment. There was no association between BBD risk and previous infertility treatments (OR = 1.21; 95% CI = 0.59–2.46), ART (OR = 1.14; 95% CI = 0.90–1.44), or OI cycles (OR = 1.13; 95% CI = 0.98–1.32). Stratification by confounding variables did not change these results. Conclusions: It seems that there is no association between BBDs in infertile women and the type, duration, or number of prior infertility treatments; however, considering the small sample size of the study, the clinical significance of this finding should not be neglected. Therefore, we consider it essential to carry out more extensive, detailed, and prospective studies to distinguish the association of BBDs with different infertility treatments and medications. [ABSTRACT FROM AUTHOR]

Introduction: Infertility related to polycystic ovary syndrome (PCOS) represents a significant challenge for women of reproductive age. Over the last few years, evidence-based medicine has driven new approaches for treating infertility in patients with PCOS, changing rapidly and deeply the clinical practice. Areas covered: The authors provide an in-depth examination of recent developments in drug treatment strategies that have impacted the clinical practice and changed the previous approach to infertility in patients with PCOS. Expert opinion: The authors identify four primary areas of interest that have impacted clinical practice in the last few years. Specifically, they discuss the current role of metformin administration in women with PCOS and infertility, the choice for using clomiphene citrate or letrozole as first-line treatment for ovulation induction, the use of new gonadotropin formulations for in vitro fertilization (IVF) program, and the elective embryo transfer in IVF cycles as golden standard treatment for patients with PCOS at high-risk for ovarian hyperstimulation syndrome. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS. Methods: Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups. Results: Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p < 0.005) and significantly greater clinical pregnancy rates per OI cycle and cumulative clinical pregnancy rates per patient (p < 0.005). Conclusion: NAC supplementation improved endocrine-metabolic parameters in PCOS mice and significantly enhanced OI efficacy with sequential LE and uFSH in women with PCOS. Therefore, NAC could be a valuable adjuvant in OI for women with PCOS. [ABSTRACT FROM AUTHOR]

Gonadotropin‐releasing hormone (GnRH) ‐supplemented extenders have emerged as a welfare‐orientated method to induce ovulation in the artificial insemination (AI) of rabbits. The main factor that limits the bioavailability of GnRH analogue on intravaginal administration is the proteolytic activity of enzymes present in rabbit seminal plasma. The use of GnRH analogues with higher biological potency would allow us to decrease their concentration in the seminal dose without compromising effectiveness. The current study was designed to assess the efficacy of various GnRH analogues concerning their ability to induce ovulation in rabbit AI. The base solution used for experimental extenders contained an aminopeptidase inhibitor. Four experimental groups were used, females from the Control group were induced to ovulate with an intramuscular administration of 1 μg of buserelin, while in the other three groups females received an intravaginal administration of 3.5 μg of buserelin (BUS), deslorelin (DES) or fertirelin (FER) within the seminal dose. Results showed that the ovulation frequency was similar in all groups studied. A concentration of 3.5 μg of the different GnRH analogues tested in this study showed similar potency in inducing ovulation in non‐lactating females, yielding comparable results in terms of pregnancy rate at birth and prolificacy. [ABSTRACT FROM AUTHOR]

Purpose: Techniques of medically assisted reproduction interact with the embryo at crucial developmental stages, yet their impact on the fetus and subsequent child's health remains unclear. Given rising infertility rates and more frequent use of fertility treatments, we aimed to investigate if these methods heighten the risk of autism spectrum disorder (ASD) in children. Methods: A population-based cohort study was conducted at Soroka University Medical Center, a tertiary referral hospital, encompassing singleton births. The incidence of ASD in offspring, incorporating either hospital or community-based diagnoses, was compared in relation to the conception method. To examine the cumulative incidence of ASD, a Kaplan–Meier survival curve was utilized. Cox proportional hazards model was employed to adjust for confounders. Results: Among 115,081 pregnancies, 0.5% involved ovulation induction (OI) and 1.7% in vitro fertilization (IVF), with the rest conceived naturally. Fertility treatments were more common in older patients and linked to more diabetes, hypertensive disorders, preterm, and cesarean deliveries. Out of 767 ASD diagnoses, offspring from OI and IVF had higher initial ASD rates (2.1% and 1.3%) than natural conceptions (0.6%). In a Cox model accounting for maternal age, ethnicity, and gender, neither OI nor IVF was significantly associated with ASD. The adjusted hazard ratios were 0.83 (95% CI 0.48–1.43) for OI and 1.34 (95% CI 0.91–1.99) for IVF. When considering fertility treatments combined, the association with ASD remained non-significant (aHR 1.11, 95% CI 0.80–1.54, p = 0.52). Conclusion: Fertility treatments, including OI and IVF, do not exhibit a significant association with heightened ASD risk in offspring. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: Ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) remains challenging, and several biomarkers have been evaluated for their ability to predict ovulation. The predictive ability of candidate biomarkers, particularly with letrozole-based therapy in infertile PCOS women, remains inconclusive as it is yet to be evaluated in a prospective study. Aim: To assess the role of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH)/FSH ratio, testosterone and free androgen index (FAI) as predictors of ovarian response to letrozole-based OI therapy during OI cycles in infertile women with PCOS from North India. Settings and Design: A prospective cohort study was conducted in a tertiary care hospital in north India. Materials and Methods: The study enrolled 80 infertile women with PCOS, diagnosed according to the Rotterdam criteria. OI was conducted using letrozole with or without human menopausal gonadotropin. Baseline endocrine and metabolic parameters, including serum AMH, FSH, LH, testosterone and FAI levels, were measured using ELISA or chemiluminescence methods on day 2 of the menstrual cycle. Follicular response to OI was monitored by transvaginal ultrasonography. Statistical Analysis Used: Descriptive and inferential statistical analyses were conducted, including Mann–Whitney, Kruskal–Wallis, Independent t -test, analysis of variance, Fisher's exact test and receiver operating characteristic curve analysis. Data were processed using Microsoft Excel and analysed with SPSS software, version 25.0. P < 0.05 was considered statistically significant. Results: Of 80 women enrolled, 74 responded to letrozole-based OI, while six were non-responders. Body mass index (BMI), serum testosterone and pre-treatment AMH levels significantly correlated with follicular response, with higher values linked to reduced responsiveness. The likelihood ratio+ (95% confidence interval) was 3.32 (2.45–5.06) for AMH, 1.97 (1.03–3.78) for BMI and 1.93 (1.22–3.08) for testosterone. The odds ratio for AMH was 2.88 (1.01–8.21) and 1.25 (1.02–1.53) for BMI. An AMH cut-off of ≤16.43 ng/mL predicted ovarian response with an AUC of 0.88. Conclusions: Pre-treatment AMH levels, along with BMI and serum testosterone, are significant predictors of ovarian response to letrozole-based OI in infertile women with PCOS. [ABSTRACT FROM AUTHOR]

Background: Poor Ovarian Response (POR) to ovarian stimulation is a challenging factor in Assisted Reproduction Technology (ART). This study aimed to compare the efficacy of a conventional antagonist with high doses of gonadotropin protocol with double stimulation protocol in females with POR. Methods: This randomized clinical trial study was conducted on 60 women aged >35 with PORS at the Avicenna Infertility Center, Tehran, Iran. The participants were randomly divided into 2 groups (n=30 /each). In group 1, from the second day of the menstrual cycle, gonadotropin started at a dose of 450-600 units. In group 2, the second day of the menstrual period began with Letrozole 5 mg every night and an oral tablet of Clomiphene citrate 50 mg every day, and from the fourth day started 150 units of gonadotrophin (Triptorelin, 0.2 mg). Results: In this study, at the end of the follicular phase, there was a significant correlation between protocol type and the number of Germinal Vesicles (GV) (p=0.04). The mean number of oocytes retrieved was 2.76±1.9 in the conventional method and 3.23±2.1 in the double stimulation group (p=0.90). The number of fertilized oocytes was 31 in the conventional protocol and 25 in the double stimulation protocol. The mean number of pregnancies that led to the fetus was 1.38±1.3 in the conventional protocol and 0.96±0.9 in the double stimulation group (p=0.018). Conclusion: The results of this study show that the embryos in the double-stimulation group were more capable of completing the pregnancy, and the double-stimulation group had a higher live birth rate. [ABSTRACT FROM AUTHOR]

Simple Summary: This review considers two key areas of reproductive management in buffaloes: assisted reproductive technology (ART) techniques, including estrous synchronization (ES) and artificial insemination (AI), and clinical approaches for functional and inflammatory reproductive diseases. It covers methods to induce ovulation and corpus luteum formation in buffaloes, and addresses prevalent reproductive pathologies like retained placenta, metritis, anestrus, and repeat breeding. This review highlights the importance of effective reproductive management strategies to enhance fertility and overall herd productivity in buffalo farming. This review aimed to bring a comprehensive analysis of key clinical strategies for enhancing reproductive efficiency in buffaloes, a species that exhibit low reproductive performance under conventional reproductive management compared to that exhibited by cattle. It considers key ART techniques including estrus synchronization for artificial insemination, and ovulation induction, highlighting their role in improving fertility and overall herd productivity. However, it also addresses common postpartum inflammatory and functional reproductive disorders, discussing their diagnosis and treatment protocols, stressing their impact on the overall reproductive outcome in buffalo farming. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether the type of frozen embryo transfer (FET) regimen — ovulation-induced regimens vs. hormone replacement therapy regimens (HRT) — is associated with live birth rates and the risk of hypertensive diseases of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS). Methods: All studies in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched using a combination of MeSH terms and keywords. Inclusion criteria included studies on women with a diagnosis of PCOS, utilization of FET, and reporting of pregnancy and/or obstetric outcomes. Studies were excluded if they were case series or conference abstracts or used other FET regimens. A random effects meta-analysis was performed. Primary outcomes include relative risk (RR) of live birth and HDP. Results: Eleven studies were included in the meta-analysis for the final review. Ovulation-induced regimens were associated with a higher live birth rate (8 studies, RR 1.14 [95% CI 1.08, 1.21]) compared to HRT regimens. The risk of HDP (3 studies RR 0.78 [95% CI 0.53, 1.15]) was not significantly different. Ovulation-induced regimens were associated with a lower miscarriage rate (9 studies, RR 0.67 [95% CI 0.59–0.76]). Rates of clinical pregnancy (10 studies, RR 1.05 [95% CI 0.99, 1.11]) and ectopic pregnancy (7 studies, RR 1.40 [95% CI 0.84, 2.33]), were not significantly different. Conclusion: This SR/MA demonstrates that for women with PCOS, ovulation-induced FET regimens are associated with higher rates of live birth and lower rates of miscarriage compared to HRT regimens. [ABSTRACT FROM AUTHOR]

Background: Polycystic Ovarian Syndrome PCOS accounts for over 75%of anovulatory infertility. Letrozole is an effective alternative to clomiphene citrate as a first line drug for ovulation induction in women with PCOS. Letrozole has a definitive role in anovulatory women who have not responded to the clomiphene citrate therapy. Aim: The objective of this study is to compare the safety and efficacy of two doses of Letrozole 2.5 mg and 5 mg as ovulation induction drug in infertile women with PCOS. Materials and methods: This was a comparative observational study. After fulfilling the selection criteria, total 90 females of PCOS were enrolled and randomly divided into two equal groups. One is treated with Letrozole 2.5mg and other is 5mg, starting from the 2nd day of menses for 5 days. Socio-demographic parameters, duration of infertility, ovulation rate, number of matured follicles, endometrial thickness, primary and secondary outcome were measured Results: There is no statistical significant difference found between Letrozole 2.5mg and Letrozole 5mg group in terms of socio-demographic and clinical characteristics (P>0.05). The ovulation rate was slightly higher in Letrozole 2.5mg group (96%) as compared to Letrozole 5mg group (92%), but not statistically significant (p>0.05). There was no significant difference in number of days to achieve follicular maturity and mean endometrial thickness at hCG administration between both groups (p>0.05). The common side effects of Letrozole therapy were nausea, dizziness and ovarian cyst formation Conclusion: This study has shown that both the doses 2.5 mg and 5 mg Letrozole have equal effectiveness for ovulation induction and it recommends the use of 2.5 mg letrozole dose for initiation of ovulation induction in PCOS. [ABSTRACT FROM AUTHOR]

UNLABELLED: PURPOSE  : To compare the cycle characteristics and outcomes of random-start-controlled ovarian stimulation (RSCOS) protocols to the outcomes of standard-start-controlled ovarian stimulation (SSCOS) cycles and to report the utility of PGT-A in these cycles. METHODS: One hundred and seventeen who underwent SSCOS and 39 who underwent RSCOS for oocyte and/or embryo cryopreservation before breast cancer chemotherapy were retrospectively evaluated. Mean number of embryos and blastocyst euploidy rates were the main outcome measures. RESULTS: A majority of RSCOS cycles were initiated in the luteal phase (66.6% luteal vs. 33.3% follicular). While the total dose of gonadotropins was significantly higher in the RSCOS (3720.8 ± 1230.0 vs. 2345.1 ± 803.6 IU; P

Introduction & Purpose of Research: Polycystic Ovary Syndrome (PCOS) is a common hormonal disorder affecting women of reproductive age. Given the high prevalence of PCOS and its impact on infertility, this research explores strategies to stimulate ovulation and improve pregnancy outcomes. To address this issue comprehensively, we specifically selected six main treatment methods: lifestyle changes, clomiphene citrate, antidiabetic drugs, gonadotropin analogues, aromatase inhibitors, and surgical approaches. Our aim was to review various studies, including meta-analyses and comparisons of methods from published texts, to gain valuable insights into the topic.

Background Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF.Methods A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3.Results A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels.Conclusions Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.

PurposeTo evaluate self-reported survey data provided by US oocyte donors on their experiences with ovarian hyperstimulation syndrome and possible correlations between OHSS severity and number of oocytes retrieved, trigger type, and prior OHSS history.MethodsAn 85-question retrospective survey was administered online. Survey questions included demographic information, reasons for donating, immediate per-cycle experiences and outcomes, perceptions of informed consent, and perceived impact of donation on long-term health. Quantitative Data for this study was collected between February 2019 and September 2020 via QualtricsXM (January 2019), an online survey platform. Follow-up interviews were also conducted. Participants were recruited via fertility clinics, egg donation agencies, and online forum. The research was approved by the University of California, San Francisco Institutional Review Board (#14-14765).ResultsOf 420 initiated US oocyte donor online surveys, 289 (68%) respondents provided detailed information on per cycle experiences with ovarian hyperstimulation syndrome, number of oocytes retrieved, and trigger type over a total of 801 cycles. On cycles where donors reported receiving GnRH agonist triggers (n = 337), they reported milder OHSS compared to cycles with hCG or dual triggers. Among donors undergoing multiple retrieval cycles, the severity of OHSS in second cycles was strongly associated with OHSS severity in first cycles.ConclusionSelf-reported OHSS in oocyte donors is lower in GnRH antagonist stimulation protocols combined with GnRHa trigger and in cycles where donors reported fewer than 30 oocytes retrieved. Donors who reported severe OHSS on a prior cycle were significantly more likely to experience severe OHSS on a subsequent cycle.

Objective: To determine the optimal letrozole regimen for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS) Design: Retrospective cohort study. Setting: Single academic fertility clinic from 2015–2022. Patient(s): A total of 189 OI cycles in 52 patients with PCOS Intervention(s): Patients were prescribed 1 of 4 letrozole regimens (group 1: 2.5 mg for 5 days, group 2: 2.5 mg for 10 days, group 3: 5 mg for 5 days, and group 4: 5 mg for 10 days). Main outcome measure(s): The primary outcome was ovulation, and secondary outcomes included multifollicular development, and clinical pregnancy rate, which were analyzed with binary logistic regression. Kaplan-Meier cumulative response curves and a Cox proportional hazard regression model were used for time-dependent analyses. Results: Mean age was 30.9 years (standard deviation [SD], 3.6) and body mass index was 32.1 kg/m2 (SD, 4.0). Group 2 (odds ratio [OR], 9.12; 95% confidence interval [CI], 1.92–43.25), group 3 (OR, 3.40; 95% CI, 1.57-7.37), and group 4 (OR, 5.94; 95% CI, 2.48–14.23) had improved ovulation rates after the starting regimen as compared with group 1. Cumulative ovulation rates exceeded 84% in all groups, yet those who received 5 mg and/or 10 days achieved ovulation significantly sooner. Multifollicular development was not increased in groups 2–4 as compared with group 1. Groups 2–4 also demonstrated improved time to pregnancy. Conclusions: Ovulation rates are improved when starting with letrozole at 5 mg and/or a 10-day extended course as compared with the frequently-used 2.5 mg for 5 days. This may shorten time to ovulation and pregnancy.

Background and objectivesPatients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse.MethodsPatients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported.ResultsOne hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI.DiscussionIn this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

Purpose: To examine the pattern of kisspeptin expression throughout the menstrual cycle in polycystic ovary syndrome (PCOS) patients under the ovulation induction and identify any possible associations with early pregnancy. Materials and methods: A prospective cohort of 80 PCOS women who expressed the desire for fertility was enrolled in this study. All of them received the ovulation induction by using letrozole. Levels of kisspeptin, luteinizing hormone (LH), and estradiol (E2) were measured at three different time points during menstruation. The early pregnancy rate was recorded for the study participants after three ovulation cycles. Results: Kisspeptin levels varied regularly during the menstrual cycle, reaching a peak on the day of hCG injection and decreasing after ovulation. There was no significant correlation between kisspeptin and LH levels. Basal kisspeptin levels decreased after letrozole treatment without a significant difference while LH and E2 levels decreased significantly. PCOS participants who became pregnant early had higher basal kisspeptin levels compared to non-pregnant PCOS patients, which had a significant difference (P = 0.006). And the average basal kisspeptin level in pregnant patients was 2293.0 ± 398.7 pg/ml, with a 95% confidence interval of 1511.5–3074.5 pg/ml. Conclusion: Kisspeptin levels in PCOS women undergoing ovulation induction showed a regular variation, which was similar with the healthy women reported in previous studies. The use of LE may result in PCOS endocrine improvement and fertility achievement. In a certain range, kisspeptin might be a potential predictor for early pregnancy in PCOS patients as people with slightly higher basal kisspeptin levels seemed more likely to be pregnant. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is a common endocrine disorder, characterized by hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. The aim of this systematic review and meta-analysis was to explore the efficacy of letrozole compared with clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome. The study protocol has been registered with PROSPERO (registration number CRD42022376611). The literature search included randomized clinical trials. We conducted our systematic literature search across three medical databases: MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. The data synthesis employed a random effects model. Out of the 1994 articles screened, 25 studies fulfilled the inclusion criteria. The letrozole group exhibited a significant increase in endometrial thickness (mean difference = 1.70, confidence interval: 0.55–2.86; I2 = 97%, p-value = 0.008). The odds of ovulation (odds ratio = 1.8, confidence interval: 1.21–2.69; I2 = 51%, p-value = 0.010) and pregnancy (odds ratio = 1.96, confidence interval: 1.37–2.81; I2 = 32%, p-value = 0.002) were significantly higher. The resistance index of the subendometrial arteries showed a significant decrease (mean difference = −0.15, confidence interval: −0.27 to −0.04; I2 = 92%, p-value = 0.030). Women diagnosed with polycystic ovarian syndrome and treated with letrozole for ovulation induction had increased ovulation and pregnancy rates and increased endometrial thickness. The lower resistance index of subendometrial arteries can enhance intrauterine circulation, creating more favorable conditions for embryo implantation and development. [ABSTRACT FROM AUTHOR]

Background: Clomiphene citrate (CC)-induced ovarian stimulation has been linked to detrimental endometrial consequences that are anti-estrogenic. Objectives: To assess the effects of sildenafil vaginal tablet combined to CC on the endometrial thickness (ET) during ovulation induction. Patients and Methods: This randomized controlled study was conducted at Departments of Obstetrics and Gynecology of Menoufia University Hospital and Alshohadaa Central Hospital. A total of 124 women were recruited. The patients were blinded to group allocation. Group I: (Clomiphene citrate (CC) alone): received clomiphene citrate (50 mg oral tablet twice daily from day 3 to day 7 of the menstrual cycle). Group II: (Clomiphene and sildenafil): received clomiphene citrate (50 mg oral tablet twice daily from day 3 to day 7 of the menstrual cycle) plus vaginal sildenafil tablets (25 mg/12h daily from day 7 up to ovulation trigger). Mean endometrial stripe thickness measured on day 13 of the cycle and pregnancy rates were the primary endpoints. Results: There were no significant differences between both groups regarding demographic, clinical and basal hormonal profiles. The mean ET measured on day 13 of menstrual cycle was statistically significantly higher among patients received clomiphene and sildenafil than those received clomiphene alone (11.09± 3.83 mm versus 9.22± 3.90 mm, p value 0.021). Also, pregnancy rates were 32.3% and 48.4% in group 1 and 2 respectively with significant differences. Conclusion: Incorporation of sildenafil to CC regimen of ovulation induction has a positive impact on endometrial stripe thickness and so pregnancy outcomes. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can an extended letrozole (LE) regimen result in a higher ovulatory rate than a conventional regimen in patients with polycystic ovary syndrome (PCOS) undergoing their first ovulation induction cycle? SUMMARY ANSWER There was no statistical difference in ovulation rate between patients with PCOS using the extended LE regimen and those using the conventional LE regimen. WHAT IS KNOWN ALREADY LE has become the first-line agent for ovulation induction. However, there is still a proportion of non-responsive cycles in patients with PCOS undergoing ovulation induction therapy with LE alone, and the extended LE regimen has been demonstrated to be a feasible method for inducing ovulation in these non-responders. Nevertheless, whether the extended regimen could be applied to all patients with PCOS as a first choice for the induction of ovulation remains to be explored. STUDY DESIGN, SIZE, DURATION This was a prospective randomized controlled trial that included 148 female patients with PCOS who underwent their first ovulation induction cycle with LE from January 2021 to October 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were randomly assigned to receive an extended (5 mg LE daily for 7 days) or conventional regimen (5 mg LE daily for 5 days) for one treatment cycle. The ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, and the rate of multiple pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE The ovulation rate among patients receiving an extended LE regimen was slightly higher than the rate with a conventional LE regimen, but the difference did not reach statistical significance in either the intention-to-treat analysis (90.54% [67/74] vs 79.73% [59/74], P  = 0.065; relative risk [95% CI]: 0.881 [0.768–1.009]) or the per-protocol analysis (90.54% [67/74] vs 84.29% [59/70], P  = 0.257; relative risk [95% CI]: 0.931 [0.821–1.055]). The number of preovulatory follicles was nearly identical in the two groups (1.39 ± 0.62 vs 1.37 ± 0.59, P  = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. With regards to the endometrial parameters, the mean endometrium thickness was slightly thicker with the conventional LE regimen compared to that with the extended LE regimen, though with no statistical difference (9.27 ± 1.72 mm vs 9.57 ± 2.28 mm, P  = 0.792). In the per-protocol analysis, the rates of clinical pregnancy (20.27% [15/74] vs 14.29% [10/70], P  = 0.343; relative risk [95% CI]: 0.705 [0.34–1.463]) and live birth (13.51% [10/74] vs 11.43% [8/70], P  = 0.705; relative risk [95% CI]: 0.846 [0.354–2.019]) did not differ significantly between treatment groups. Moreover, all conceptions were singletons without neonatal defects. LIMITATIONS, REASONS FOR CAUTION The major concerns regarding this study are its single-center and open-label nature. Additionally, the limited number of lean patients with PCOS with a mean body mass index of 23–25 kg/m2 enrolled in our trial also restricted the generalizability of our findings. WIDER IMPLICATION OF THE FINDINGS A change from the standard strategy of ovulation induction in patients with PCOS is not advisable, because a statistically superior effect of the extended LE regimen over a conventional regimen was not detected. The extended LE regimen could be applied with caution in a specific population who failed to respond to a conventional regimen rather than all the patients with PCOS during ovulation induction. Additional prospective trials with larger sample sizes and different PCOS subgroups are needed to assess the ovulatory effects of various LE treatment durations. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Shanghai First Maternity and Infant Hospital, affiliated with Tongji University School of Medicine (grant numbers: 2023B03 to Y.F. 2023B18 to X.Z. and 2020RC02 to Y.F.). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER Chinese Clinical Trial Registry (ChiCTR2100042082). TRIAL REGISTRATION DATE 13 January 2021. DATE OF FIRST PATIENT'S ENROLMENT 21 January 2021. [ABSTRACT FROM AUTHOR]

Summary: This comprehensive guideline, developed by a representative group of UK‐based medical experts specialising in haemoglobinopathies, addresses the management of conception and pregnancy in patients with thalassaemia. A systematic search of PubMed and EMBASE using specific keywords, formed the basis of the literature review. Key terms included "thalassaemia," "pregnancy," "Cooley's anaemia," "Mediterranean anaemia," and others, covering aspects such as fertility, iron burden and ultrasonography. The guideline underwent rigorous review by prominent organisations, including the Endocrine Society, the Royal College of Obstetricians and Gynaecologists (RCOG), the United Kingdom Thalassaemia Society and the British Society of Haematology (BSH) guideline writing group. Additional feedback was solicited from a sounding board of UK haematologists, ensuring a thorough and collaborative approach. The objective of the guideline is to equip healthcare professionals with precise recommendations for managing conception and pregnancy in patients with thalassaemia. [ABSTRACT FROM AUTHOR]

Objective Pituitary stalk interruption syndrome (PSIS) is a rare cause of congenital hypopituitarism. Limited data exist on the gonadotropic status and fertility of adult women with PSIS. Our study aims to describe pubertal development and the evolution of gonadotropic function and fertility in adult women with PSIS. Design A retrospective multicentric French study. Methods We described gonadotropic function in 56 adult women with PSIS from puberty onward. We compared live birth rates per woman with PSIS with age-matched controls from the large French epidemiological cohort (CONSTANCES). Additionally, we assessed height, body mass index (BMI), blood pressure, other metabolic parameters, and socioeconomic status. Results and Conclusions Among 56 women with PSIS, 36 did not experience spontaneous puberty. Of these, 13 underwent ovarian stimulation, resulting in 7 women having a total of 11 children. In the subgroup with spontaneous puberty (n = 20), 4 had a total of 8 pregnancies, while 6 developed secondary gonadotropic deficiency. Women with PSIS had fewer children than controls (0.33 vs 0.63, P =.04). Median height was also lower (160.5 vs 165.0 cm, P <.0001). Although mean blood pressure was lower in women with PSIS compared with controls (111.3/65.9 ± 11.2/8.1 vs 118.7/72.1 ± 10.1/7.7 mmHg, P <.001), there were no significant differences in other metabolic parameters, notably BMI and lipid profile. Employment/academic status was not different in the 2 groups, but fewer women with PSIS were in relationships (42% vs 57.6% in controls, P =.02). The fertility prognosis in patients with PSIS needs optimization. Patients should be informed about the likelihood of declining gonadotropic function over time. [ABSTRACT FROM AUTHOR]

Background: Various protocols have been approved to improve the response rate leading to successful fertilizationin poor ovarian responders (PORs). The application of double ovarian stimulation (DuoStim) in the follicular andluteal phases of the same ovarian cycle has been shown as an intriguing option to achieve more oocyte retrievals inthe shortest time. The aim of the current study, is to compare the outcomes of different protocols, minimal stimulation(MS) and Duostim.Materials and Methods: This randomized clinical trial was performed on 42 in vitro fertilization (IVF) candidateswith POR diagnosis. Patients were classified into two equal groups and treated with the DuoStim protocol and MSprotocol. The IVF outcomes, including retrieved follicles, oocytes, metaphase II (MII) oocytes and embryos, werecompared between these groups.Results: The patients’ characteristics including age, anti-mullerian hormone (AMH), follicle-stimulating hormone(FSH), luteinizing hormone (LH), and antral follicle count (AFC) were collected and compared. It showed there wasno significant difference between the two groups' baseline characteristics (P>0.05). We observed that the DuoStimprotocol resulted in a significantly higher score in comparison with the MS protocols, including the number of follicles(6.23 ± 2.93 vs. 1.77 ± 1.66, P

To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF), and unassisted conception to the increase in national plural births in the United States, a significant contributor to adverse maternal and infant health outcomes. National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967–2021, after introduction of Clomiphene Citrate in the United States) and the National Assisted Reproductive Technology Surveillance System (1997–2021), respectively. Not applicable. Not applicable. Not applicable. In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949–1966 and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts. From 1967–2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1,000 live births), then declined to 31.2/1,000 live births; the triplet and higher order birth rate increased 6.7-fold to a 1998 high (1.9/1,000 live births), then declined to 0.8/1,000 live births. In 2021, the contribution of unassisted conception among women aged <35 years to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women aged ≥35 years (16.8%), and IVF (7.6%). During 2009–2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women aged <35 and ≥35 years has increased, and the contribution of IVF has decreased. Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age of ≥35 years is a significant contributor to the national plural birth increase. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether utilization of assisted reproductive technology following clearance of endometrial intraepithelial neoplasia (EIN) or early endometrial cancer (EC) shortens time to conception (TTC) and reduces recurrence. Patients aged 18 to 45 with EIN or early EC who achieved pathologic response following progesterone treatment were identified via retrospective chart review. Study groups included patients who pursued ovulation induction (OI), in vitro fertilization (IVF), and spontaneous pregnancy. Primary outcomes were TTC and recurrence rate. Three hundred forty-six charts were reviewed, with 86 patients meeting inclusion criteria and 53 attempting pregnancy. Of those 53 patients, 11 became pregnant and seven had a live birth. Median times to pregnancy were 183 days for IVF, 54 days for OI, and 347 days for spontaneous conception (p < 0.05). No differences were seen in recurrence or progression based on attempted pregnancy method, nor with duration of fertility treatment. Forty-two of 86 patients (49%) were lost to follow-up. For patients with a history of treated EIN or EC, OI may decrease TTC. Larger prospective studies are needed to definitively answer this question. Although no differences in recurrence or progression were identified, the significant loss to follow-up rate in this study is concerning and warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose: To identify and characterise appropriate comparison groups for population studies of health outcomes in ART-conceived births: ovulation induction (OI), subfertile untreated and fertile natural conceptions. Our secondary objective was to examine whether known risks of pregnancy complications and adverse birth outcomes in ART births are elevated in comparison with subfertile (untreated and OI) conception groups. Methods: We linked State and Commonwealth datasets to identify all live and stillbirths (≥ 20 weeks) in Western Australia from 2003 to 2014 by method of conception. Demographic characteristics, maternal pre-existing conditions, adverse obstetric history and pregnancy complications were compared across conception groups. Generalised estimating equations were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CI) for pregnancy complications and birth outcomes in singletons. Results: We identified 9456 ART, 3870 OI, 11,484 subfertile untreated and 303,921 fertile naturally conceived deliveries. OI and subfertile untreated groups more closely resembled the ART group than the fertile group; however, some differences remained across parity, maternal age, pre-existing conditions and obstetric history. In multivariate analyses, ART singletons had greater risks of placental problems (e.g. placenta praevia aRR 2.42 (95% CI 1.82–3.20)) and adverse birth outcomes (e.g. preterm birth aRR 1.38 (95% CI 1.25–1.52)) than the subfertile untreated group, while OI singletons were more similar to the subfertile group with higher risk of preeclampsia and gestational diabetes. Conclusion: OI and subfertile untreated conception groups offer improved options for interpreting health outcomes in ART births. Pregnancy complications (particularly placental disorders) and adverse outcomes at delivery are more common following ART. [ABSTRACT FROM AUTHOR]

Background: Various protocols have been approved to improve the response rate leading to successful fertilization in poor ovarian responders (PORs). The application of double ovarian stimulation (DuoStim) in the follicular and luteal phases of the same ovarian cycle has been shown as an intriguing option to achieve more oocyte retrievals in the shortest time. The aim of the current study is to compare the outcomes of different protocols, minimal stimulation (MS) and Duostim. Materials and Methods: This randomized clinical trial was performed on 42 in vitro fertilization (IVF) candidates with POR diagnosis. Patients were classified into two equal groups and treated with the DuoStim protocol and MS protocol. The IVF outcomes, including retrieved follicles, oocytes, metaphase II (MII) oocytes and embryos, were compared between these groups. Results: The patients' characteristics including age, anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and antral follicle count (AFC) were collected and compared. It showed there was no significant difference between the two groups baseline characteristics (P>0.05). We observed that the DuoStim protocol resulted in a significantly higher score in comparison with the MS protocols, including the number of follicles (6.23 ± 2.93 vs. 1.77 ± 1.66, P<0.001), retrieved oocytes (3.86 ± 2.57 vs. 1.68 ± 1.58, P=0.002), MII oocytes (3.36 ± 2.42 vs. 1.27 ± 1.27, P=0.001) and obtained embryos (2.04 ± 1.64 vs. 0.77 ± 0.86, P=0.003). Conclusion: The DuoStim protocol is a favourable and time saving plan that is associated with more oocytes in a single stimulation cycle. The DuoStim protocol significantly can result in more frequent MII oocytes and embryos. We figured that the higher number of oocytes and embryos might have led to a higher rate of pregnancy (registration number: IRCT20200804048303N1). [ABSTRACT FROM AUTHOR]

To describe the serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction in women treated with clomiphene and metformin. Secondary analysis of randomized controlled trial. Not applicable. A total of 333 women with anovulatory infertility attributed to PCOS who participated in the double-blind randomized trial entitled the Pregnancy in Polycystic Ovary Syndrome I (PPCOS I) study (registration number, NCT00068861) who had serum samples from baseline laboratory testing available for further serum analysis were studied. Not applicable. The association between the baseline AMH levels in each of the 3 treatment groups and ovulation, pregnancy, and live birth rates were assessed. A total of 322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL (range 0.1–43.0 ng/mL). With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10% (odds ratio, 0.90; 95% confidence interval, 0.86–0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared with those with a normal baseline AMH concentration (<4 ng/mL) (odds ratio, 0.23; 95% confidence interval, 0.05–0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance score. Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders. These AMH values in well-phenotyped individuals with PCOS add to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with ovulation induction with clomiphene, clomiphene + metformin, and metformin. The original trial from which this analysis is derived was entitled "Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome" and was registered on ClinicalTrials.gov as number NCT00068861. The URL for the trial is https://clinicaltrials.gov/study/NCT00068861. The first subject was enrolled in November 2002. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects of a baseline ovarian cyst on ovulation induction/intrauterine insemination (OI/IUI) cycle outcomes. Methods: A retrospective cohort analysis of 270 patients and 461 OI/IUI cycles performed between 2011 and 2021 was performed. The exposure variable was a simple appearing ovarian cyst diagnosed at baseline ultrasound measuring ?10?mm with an estradiol level

Anti-Mullerian hormone is a robust marker of ovarian reserve and ovarian response in in vitro fertilisation (IVF). However, its role extends beyond improving the safety of IVF by aiding in choosing appropriate protocols and dosing. This review looks at the value of pre-treatment anti-Mullerian hormone (AMH) value in choosing the appropriate modality of treatment and its predictive ability for the outcomes of such treatment. It briefly addresses the factors that may modulate AMH levels and make clinical decision-making challenging.

PurposeTo investigate if breast cancer stage and grade affect fertility preservation outcomes.MethodsWe performed a retrospective cohort study that included premenopausal women with breast cancer undergoing fertility preservation diagnosed between January 2011 and January 2019. The primary outcome measure was the number of mature oocytes (MII) per antral follicle count (AFC). Secondary outcome measures included total oocytes retrieved, total mature oocytes retrieved, and greater than 10 mature oocytes preserved. Univariate and multivariate models were used to assess the association of low vs. high stage (low stage I-II and high stage III-IV) and grade I vs. grade II/III with each outcome, with adjustment for confounders.ResultsA total of 267 premenopausal breast cancer patients undergoing fertility preservation were included in our study, with the majority presenting with low stage (N = 215, 80.5%), grade II/III (N = 235, 88.1%) disease. Baseline AFC, total gonadotropin dose, days of stimulation, and follicles [Formula: see text] 13 mm on the day of trigger did not differ by stage or grade. After adjusting for age, BMI, and baseline AFC, we found that the mean MII per AFC did not differ by stage (1.0 vs. 1.1, P = 0.3) or grade (1.0 vs. 1.0, P = 0.92). Similarly, total oocytes retrieved, total MII retrieved, and percentage of patients who were able to preserve greater than 10 MII did not differ by breast cancer stage or grade (all P > 0.2).ConclusionBreast cancer grade and stage do not impact ovarian stimulation or fertility preservation outcome.

STUDY QUESTION: What are the comparative pregnancy outcomes in women who receive up to six consecutive cycles of ovulation induction with letrozole versus clomiphene citrate? SUMMARY ANSWER: The risks of pregnancy, livebirth, multiple gestation, preterm birth, neonatal intensive care unit (NICU) admission and congenital malformations were higher for letrozole compared with clomiphene in participants with polycystic ovarian syndrome (PCOS), though no treatment differences were observed in those with unexplained infertility. WHAT IS KNOWN ALREADY: Randomized trials have reported higher pregnancy and livebirth rates for letrozole versus clomiphene among individuals with PCOS, but no differences among those with unexplained infertility. None of these trials were designed to study maternal or neonatal complications. STUDY DESIGN, SIZE, DURATION: We emulated a hypothetical trial of the comparative effectiveness of letrozole versus clomiphene citrate for ovulation induction among all women, then stratified by PCOS and unexplained infertility status. We used real-world data from a large healthcare claims database in the USA (2011-2015). PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed data from 18 120 women who initiated letrozole and 49 647 women who initiated clomiphene during 2011-2014, and who were aged 18-45 years with no history of diabetes, thyroid disease, liver disease or breast cancer and had no fertility treatments for 3 months before trial initiation. The treatment strategies were clomiphene citrate or letrozole for six consecutive cycles. The outcomes were pregnancy, livebirth, multiple gestation, preterm birth, small for gestational age (SGA), NICU admission and major congenital malformations. We estimated the probability of each outcome under each strategy via pooled logistic regression and used standardization to adjust for confounding and selection bias due to loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: The estimated probabilities of pregnancy, livebirth and neonatal outcomes were similar under each strategy, both overall and among individuals with unexplained infertility. Among women with PCOS, the probability of pregnancy was 43% for letrozole vs 37% for clomiphene (risk difference [RD] = 6.0%; 95% CI: 4.4, 7.7) in the intention-to-treat analyses. The corresponding probability of livebirth was 32% vs 29% (RD = 3.1%; 95% CI: 1.5, 4.8). In per protocol analyses, the risk of multiple gestation was 19% vs 9%, the risk of preterm birth was 20% vs 15%, the risk of SGA was 5% vs 3%, the risk of NICU admission was 22% vs 16% and the risk of congenital malformation was 8% vs 2% among those with a livebirth. LIMITATIONS, REASONS FOR CAUTION: We cannot completely rule out the possibility of residual confounding by body mass index or duration of infertility. However, we adjusted for proxies identified in administrative data and results did not change. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that for women with unexplained infertility, the two treatments result in comparable probabilities of a livebirth. For women with PCOS, letrozole appears slightly more effective for attaining a livebirth. Neonatal outcomes were similar for the two treatments among women with unexplained infertility; we did not confirm the hypothesized higher risk of adverse neonatal outcomes for clomiphene versus letrozole. The risks of adverse neonatal outcomes were slightly greater among women with PCOS who were treated with letrozole versus clomiphene. It is likely that these effects are partially mediated through an increased risk of multiple gestation among women who received letrozole. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institute of Child Health and Human Development (R01HD088393). Y.-H.C. reports grants from the American Heart Association (834106) and NIH (R01HD097778). P.R. reports grants from the National Institutes of Health. J.H. reports grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the California Health Care Foundation during the conduct of the study; and consulting for several health care delivery organizations including Cambridge Health Alliance, Columbia University, University of Southern California, Community Servings, and the Delta Health Alliance. S.H.-D. reports grants from the National Institutes of Health and the US Food and Drug Administration during the conduct of the study; grants to her institution from Takeda outside the submitted work; consulting for UCB (biopharmaceutical company) and Roche; and being an adviser for the Antipsychotics Pregnancy Registry and epidemiologist for the North American Antiepileptics Pregnancy Registry, both at Massachusetts General Hospital. M.A.H. reports grants from the National Institutes of Health and the U.S. Veterans Administration during the conduct of the study; being a consultant for Cytel; and being an adviser for ProPublica. TRIAL REGISTRATION NUMBER: N/A.

Abstract Background The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction. Methods A randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A “combination group” received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a “CC-alone group” received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events. Results One hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group. Conclusions Our study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study. Trial registration The study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.

Objective To explore the safety of fertility-sparing surgery and the selection of ovulation induction protocols in patients with early-stage borderline ovarian tumors (BOTs). Methods Clinical data were collected from four patients with early-stage BOTs who underwent fertility-sparing surgery and later sought treatment for infertility with assisted reproduction and successfully delivered in Xinhua Hospital Affiliated to School of Medicine in Shanghai Jiao Tong University from January 2015 to December 2021. The postoperative follow-up and assisted reproduction of the patients were reviewed in combination with the literature. The estrogen levels of patients on HCG day were compared between antagonist protocol, agonist protocol, and letrozole mild stimulation protocol. Results Two of the four patients with early-stage BOTs relapsed after fertility-sparing surgery. The pa-thological type of relapse was BOTs without malignant transformation. No recurrence was observed during follow-up after the se-cond operation. All four patients underwent assisted reproduction and achieved delivery. One of the patients who experienced relapse underwent oocyte retrieval before the second surgery and achieved pregnancy through frozen embryo transplantation after the surgery. Three out of four patients used letrozole mild stimulation protocol (two of them achieved pregnancy, while the other patient switched to agonist protocol after failing to retrieve oocytes and subsequently became pregnant). The remaining patient used anta-gonist protocol and achieved pregnancy. Compared with the antagonist and agonist protocols, letrozole mild stimulation protocol had the lowest serum estrogen level on the HCG day. Conclusion Fertility-sparing surgery for patients with early-stage BOTs is safe and feasible. Oocyte retrieval can be considered in case of recurrence before reoperation. Letrozole mild stimulation protocol provides a relatively safe option with minimal adverse effects on the ovaries.

Background In the field of assisted reproductive technology, medical cost of patients is increasingly considered as an important reference for making treatment protocols, while domestic health economics researches are rarely reported on the cost-effectiveness of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and short-acting GnRH agonist (GnRH-a) long protocol in fresh embryo transfer. Objective To analyse the cost-effectiveness of the clinical outcomes of GnRH-ant and GnRH-a protocols in fresh embryo transfer based on propensity score matching (PSM) . Methods A total of 1 971 patients treated with 2 117 cycles of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) at the Reproductive Medicine and Genetics Center of the People's Hospital of Guangxi Zhuang Autonomous Region from 2016 to 2018 were selected and divided 422 patients with 432 cycles in the GnRH-ant group and 1 549 patients with 1 685 cycles in the GnRH-a group according to the protocols of controlled ovarian hyperstimulation (COH). Baseline data 〔including female age, type and duration of infertility, BMI, age at menarche, number of pregnancies, follicle stimulating hormone (FSH), basal estradiol (E2), basal luteinizing hormone (LH), basal progesterone, antral follicle count (AFC), etc.〕, therapeutic indicators 〔including COH protocols, gonadotropin (Gn) durarion, total Gn dosage, E2, LH, progesterone level and endometrial thickness on the trigger day, number of retrieved and mature oocytes, fertilization methods, number of transferable embryos, high-quality embryos and transferred embryos, etc.〕 and the clinical outcomes〔including unpregnancy, miscarriage, ectopic gestation, live birth (LB) 〕 were collected from the electronic medical record system and the 1∶1 PSM was performed using R 4.1.1 software with caliper value of 0.2. Cost-effectiveness analysis was performed on the two groups after PSM, sensitivity analysis was applied to verify the robustness of the study findings. Results There were significant differences in female age, BMI, basal FSH, LH, and AFC between the two groups before PSM (P0.05). Therapeutic indicators including Gn duration, Gn dosage, E2 and endometrial thickness on the trigger day, number of retrieved and mature oocytes were lower in the GnRH-ant group than GnRH-a group, while LH level on the trigger day was higher in the GnRH-ant than the GnRH-a group (P

Study question: In infertile women with polycystic ovary syndrome (PCOS), is the sequential use of letrozole 2.5 mg/follicle stimulating hormone(FSH) more effective than letrozole 5 mg/FSH in stimulating ovulation and promoting pregnancy? Research design and methods: The study was designed as a prospective, single-center, randomized, controlled pragmatic clinical trial. 220 infertile women between the ages of 20 and 40, who matched the Rotterdam criteria for PCOS and had no other identified reasons for infertility were enrolled from April 2023 to July 2023. The participants were randomly assigned to two groups in a 1:1 ratio. One group received 2.5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110), while the other group received 5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110). The duration of FSH treatment varied depending on the follicular development stage. Each participant underwent one to three treatment cycles until achieving pregnancy. The primary outcome was the cumulative pregnancy rate of all the participants. Secondary outcomes included characteristics and clinical pregnancy rates of all the intervention cycles. Results: For all 220 participants, the sequential letrozole 2.5 mg/FSH treatment group had a significantly higher cumulative pregnancy rate compared to the letrozole 5 mg/FSH treatment group (72.7% versus 59.1%, RR (95%CI) = 1.23 (1.02, 1.49), P-value = 0.033). For all 468 intervention cycles, letrozole 2.5 mg/FSH group had a significantly higher clinical pregnancy rate than the letrozole 5 mg/FSH group (36.2% versus 26.3%, Pvalue = 0.021), no statistically significant differences were observed in ovulation rates or adverse effects. Conclusions: The data indicate that the sequential letrozole 2.5mg/FSH protocol may be more effective than the sequential letrozole 5mg/FSH protocol for promoting pregnancy in infertile women with PCOS. [ABSTRACT FROM AUTHOR]

In assisted reproductive technology, it is very important to prevent the premature endogenous luteinizing hormone (LH) peak in process of controlled ovarian stimulation. Traditional controlled ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) analogues (GnRH agonists or antagonists) to inhibit the level of endogenous LH have many disadvantages such as high cost and inconvenient use. Progestin-primed ovarian stimulation (PPOS) protocol has been proved to achieve good clinical outcomes in various populations by the negative feedback effect of exogenous progesterone on pituitary gland to inhibit LH level, and its offspring safety has also been preliminarily confirmed. In this paper, the mechanism of PPOS, application of different exogenous progesterone drugs, application effects of different populations and offspring safety of PPOS were reviewed. [ABSTRACT FROM AUTHOR]