Polycystic Ovary Syndrome Women Research Articles

The regulatory roles of Smad2/3 protein and SMURF2 gene expression in granulosa cells of germinal vesicle and metaphase II oocytes in polycystic ovarian syndrome: A case-control study.

The impaired functions of granulosa cells (GCs) in the delayed development and immaturity of oocytes have been reported in polycystic ovary syndrome (PCOs). Even with ovarian stimulation, a large number of oocytes in these patients are still in the stage germinal vesicle (GV). The levels of Smad2/3, phosphorylated Smad2/3 (P-Smad2/3), the expression of SARA, Smad4, and SMURF2 genes in the GCs surrounding metaphase II (MII) or GV oocytes in PCOs women were investigated. GCs of MII and GV oocytes were isolated from 38 women with PCOs and the expression levels of SARA, Smad4, and SMURF2 in surrounding GCs of MII and GV oocytes were determined using reverse-transcription polymerase chain reaction. Also, Smad2/3 and P-Smad2/3 proteins were determined using western blotting. The expression level of SMURF2 was significantly higher in GCs surrounding GV oocytes compared with that of GCs encompassing MII oocytes (p 0.001). At the same time, no significant differences were observed in SARA and Smad4 expression levels in GCs surrounding GV and MII oocytes. A lower level of P-Smad2/3 was also found in GCs GV oocytes compared with GCs of MII oocytes (p 0.001). It seems that P-Smad2/3 plays a role in oocyte development, and the downregulation of this protein is associated with a defect in the maturation of GV oocytes. On the other hand, the upregulation of the SMURF2 gene also affects the growth process of GCs and the maturation of GV oocytes.

Role of Lipid Ratios in Determining the Insulin Resistance in Polycystic Ovary Syndrome Women at a Tertiary Care Hospital in South India

Role of Lipid Ratios in Determining the Insulin Resistance in Polycystic Ovary Syndrome Women at a Tertiary Care Hospital in South India

Metformin administration during pregnancy tends to reduce the risk of gestational diabetes mellitus and improve pregnancy outcomes in previously infertile women with polycystic ovary syndrome who become pregnant.

Metformin reduces incidences of miscarriage and preterm delivery in polycystic ovary syndrome (PCOS) women, but its impact on gestational diabetes mellitus (GDM) is conflicting. Hence, this study set up selection criteria to include previously infertile women with PCOS but without pre-existing DM who became pregnant, aiming to minimize confounders and investigate the influence of metformin on GDM, miscarriage, and preterm delivery. This study included 195 previously infertile women with PCOS who became pregnant. They were divided into metformin (receiving metformin during pregnancy) and control (not receiving metformin) groups without intervention. Metformin group tended to have a lower incidence of GDM versus control group (13.3% versus 23.3%, P = 0.070). A logistic regression model adjusted for all baseline characteristics (demographics, infertile duration, and diabetes mellitus-related features) showed that metformin was associated with a decreased probability of GDM (odds ratio (OR): 0.426, P = 0.037). Metformin group showed a similar incidence of miscarriage (6.7% versus 11.1%, P = 0.273), but decreased incidences of preterm delivery (not statistically significant) (6.7% versus 13.3%, P = 0.091) and miscarriage or preterm delivery (13.3% versus 24.4%, P = 0.046) versus control group. A logistic regression model adjusted for all the aforementioned features revealed that metformin was related to a lower risk of miscarriage or preterm delivery (OR: 0.417, P = 0.040). Fetal outcomes, including birth weight (P = 0.245) and the incidence of 5min-Apgar score ≤ 7 (P = 0.702), were similar between groups. Metformin administration during pregnancy may reduce GDM, miscarriage, and preterm delivery risks without adverse effects on fetal outcomes in previously infertile women with PCOS.

The Relationship between Thyroid Hormones and Insulin Resistance in Polycystic Ovary Syndrome Women.

This study aimed to investigate the changes in thyroid hormones in the serum of patients with polycystic ovary syndrome (PCOS) and their correlation with insulin resistance. This is a retrospective study. 84 patients having insulin resistance and 76 patients without insulin resistance were included. 90 women without history of PCOS were selected as a healthy control group. This study was conducted at Shijiazhuang Fourth Hospital. Blood samples were collected from each group on days 3-5 of their menstrual cycle, and their triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were analyzed and compared between groups. We investigated the changes of serum thyroid hormones in patients with PCOS and their correlation with insulin resistance. We found that serum levels of T3 and T4 were significantly decreased, while TSH levels were significantly increased in PCOS patients compared with HCs. Moreover, we found that patients with insulin resistance had significantly lower levels of serum T3 and T4 and higher levels of TSH compared to those PCOS participants without insulin resistance. This study was a retrospective and single-center study, which had selection bias, information bias, and confounding variables may affect the accuracy and reliability of the conclusion. Insulin resistance negative correlates with their serum T3, T4, and positive correlates with their TSH levels. Our results develop a combined test model with the serum T3, T4, and TSH levels for the clinical diagnosis of insulin resistance in PCOS women.

Effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome: a randomized controlled trial

ObjectiveThe aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS).MethodsA total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters.ResultsThe serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P < 0.05). The BMI, WHR, insulin concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (P < 0.05). The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower compared with control group (obesity) (P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (P < 0.05). No significant difference was observed in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (P > 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05).ConclusionVitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance.

Differential Prevalence of Depression Symptoms in Obese Versus Non-obese Women with Polycystic Ovary Syndrome

Background: Polycystic ovarian syndrome (PCOS) is a prevalent chronic endocrine disorder that effects on women ovaries. It is characterized by mental health issues including depression and obesity. Hence the purpose of this particular study was to determine whether depressive symptoms were more common in obese PCOS women or in non-obese women. Methodology: The current study involved a cross-sectional design where the participants were 200 women with PCOS, and they were further divided into the obese and non-obese groups on the bases of their BMI. The depressive symptoms were assessed with the Beck Depression Inventory – II (BDI-II). Raw data were interpreted bio- statistically by applying chi-squared test and logistic regression to determine the association between symptoms of obesity and depression by using a software known as SPSS. Results: The women of obese group with polycystic ovarian syndrome had a mean score of moderate (35.12± 0.01) and severe depressed symptoms than the non-obese PCOS women (22.11± 0.03). The applications of the logistic regression model revealed that the obesity could be considered to have a statistically significant (P≤0.05) impact on the depression symptoms. Conclusion: Through the research that the study carried out it was discovered that obesity could be causatively related to depression in women with PCOS. These results point to the importance of the proposed features of PCOS as a complex disorder that requires a holistically oriented treatment approach that involves not only physical but also psychological factors.

Investigation of some fertility indicators in Iraqi women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous, multigenic disorder in women of childbearing age with multiple consequences. The exact mechanism of PCOS is not yet fully understood; There are several factors have a role such as genetic, environmental, nutritional, metabolic and other interactions Therefore, the existing study designed to estimate the levels of some biochemical tests and the sex hormones that have a role in PCOS progress. 100 Iraqi women were agreed to participate in the current study, divided into two groups included 50 clinically diagnosed with PCOS women that compared with 50 healthy women without PCOS as a control group (CTRL). The results showed different significant differences of the studied parameters between the PCOS and the CTRL. There was a significant increased level of FBG, HbA1c, insulin resistant, TG and LDL in the PCOS group in comparison to the CTRL, while a significant decreased level of HDL was appeared in PCOS group in comparison to the CTRL. Regarding the results of sex hormones, there were significant increased levels of LH, FSH, testosterone, estradiol hormones in the PCOS group in comparison to the CTRL. In addition, the results of thyroid hormones appeared a significant increased level of T3 hormone in the PCOS group in comparison to the CTRL. Also, the results of leptin hormone showed a significant increased level in the PCOS group in comparison to the CTRL. In conclusion, there was a significant relationship between FBG, HbA1c, insulin resistant, TG, LDL, HDL, LH, FSH and T3 parameters with PCOS.

دور داء السكري في متلازمة تكيس المبايض PCOS

The study focused on the insulin and its relationship with the Polycystic Ovary Syndrome (PCOS) in women. Where was it collected 44 samples of PCOS women and 46 samples as a control group. The results showed a significant decrease in progesterone at (P = 0.001), in women with PCOS. The findings in this study revealed the presence of a link between high insulin levels and polycystic ovarian syndrome, the statistical results demonstrate a positive significant association between insulin and estrogen at (p=0.001), and also found a significant negative correlation between other clinical parameter with insulin at, for those with the syndrome, due to the high level of insulin in their blood and the inability of female hormones and Insulin Antibody (AIA), to play their role in controlling the insulin and blood sugar level. Finally, the study showed that there is a new strong relationship between diabetes on PCOS and abortion.

The Efficacy and Safety of DLBS3233, A Combined Bioactive Fraction of Cinnamomum burmanii and Lagerstroemia speciosa Plants on The Endocrine-Metabolic Profile of Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

Case Series: Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome.

Do hyperactive kisspeptin neurons contribute to abnormally high LH secretion and downstream hyperandrogenemia in polycystic ovary syndrome (PCOS)-like conditions and can inhibition of kisspeptin neurons rescue such endocrine impairments? Targeted inhibition of endogenous kisspeptin neuron activity in a mouse model of PCOS reduced the abnormally hyperactive LH pulse secretion and hyperandrogenemia to healthy control levels. PCOS is a reproductive disorder characterized by hyperandrogenemia, anovulation, and/or polycystic ovaries, along with a hallmark feature of abnormal LH hyper-pulsatility, but the mechanisms underlying the endocrine impairments remain unclear. A chronic letrozole (LET; aromatase inhibitor) mouse model recapitulates PCOS phenotypes, including polycystic ovaries, anovulation, high testosterone, and hyperactive LH pulses. LET PCOS-like females also have increased hypothalamic kisspeptin neuronal activation which may drive their hyperactive LH secretion and hyperandrogenemia, but this has not been tested. Transgenic KissCRE+/hM4Di female mice or littermates Cre- controls were treated with placebo, or chronic LET (50 µg/day) to induce a PCOS-like phenotype, followed by acute (once) or chronic (2 weeks) clozapine-N-oxide (CNO) exposure to chemogenetically inhibit kisspeptin cells (n = 6 to 10 mice/group). Key endocrine measures, including in vivo LH pulse secretion patterns and circulating testosterone levels, were assessed before and after selective kisspeptin neuron inhibition and compared between PCOS groups and healthy controls. Alterations in body weights were measured and pituitary and ovarian gene expression was determined by qRT-PCR. Acute targeted inhibition of kisspeptin neurons in PCOS mice successfully lowered the abnormally hyperactive LH pulse secretion (P < 0.05). Likewise, chronic selective suppression of kisspeptin neuron activity reversed the previously high LH and testosterone levels (P < 0.05) down to healthy control levels and rescued reproductive gene expression (P < 0. 05). N/A. Ovarian morphology was not assessed in this study. Additionally, mouse models can offer mechanistic insights into neuroendocrine processes in PCOS-like conditions but may not perfectly mirror PCOS in women. These data support the hypothesis that overactive kisspeptin neurons can drive neuroendocrine PCOS-like impairments, and this may occur in PCOS women. Our findings complement recent clinical investigations using NKB receptor antagonists to lower LH in PCOS women and suggest that pharmacological dose-dependent modulation of kisspeptin neuron activity may be a valuable future therapeutic target to clinically treat hyperandrogenism and lower elevated LH in PCOS women. This research was supported by NIH grants R01 HD111650, R01 HD090161, R01 HD100580, P50 HD012303, R01 AG078185, and NIH R24 HD102061, and a pilot project award from the British Society for Neuroendocrinology. There are no competing interests.

ELEVATE SOME TYPES OF ADIPOKINES IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS)

The current work aimed to estimate some types of Adipokines (Leptin, adiponectin and the resistin) in PCOS women. The participants belong to both PCOS women and healthy women were selected and examined in Azadi teaching hospital at September 2021 to February 2022. 80 patients with 30 controls were used in this study. The current outcomes show the concentration of Leptin in PCOS patients, where concentration of Leptin demonstrated significant (P &lt;0.05) elevate in PCOS women compared with healthy women. Adiponectin concentration in PCOS women indicated significant (P &lt;0.05) reduce compared with healthy women. Resistin concentration in PCOS women indicated significant (P &lt;0.05) raise compared with healthy women. So, based on this findings, PCOS lead to significant (P &lt;0.05) differences in concentration of some types of Adipokines.

P-691 Effect of body mass index on early and late pregnancy loss in women with polycystic ovary syndrome undergoing in vitro fertilization and embryo transfer

Abstract Study question Are early and late pregnancy loss both affected by elevated body mass index (BMI) in women with polycystic ovary syndrome (PCOS) undergoing IVF-ET? Summary answer Late pregnancy loss but not early pregnancy loss was adversely affected by elevated BMI in women with PCOS undergoing IVF-ET. What is known already PCOS, the most common endocrine disorder in women of reproductive age, affects 5–18% of women. Obesity appears to be closely associated with PCOS. High BMI of the women with PCOS has been clearly associated with pregnancy loss. However, available data are limited for distinguishing between early and late pregnancy loss in PCOS women with different BMI and age. We performed a large cohort study of PCOS women conceived after IVF-ET to access the risk of early and late pregnancy loss. Study design, size, duration A retrospective cohort study of 3213 pregnancies after IVF-ET in women with PCOS from January 2015 to October 2022. Participants/materials, setting, methods The participants were the PCOS women with a positive human chorionic gonadotropin (hCG) after IVF-ET treatment in the reproductive centre of an university hospital. We studied early (≤12 weeks and biochemical pregnancy loss included) and late (&amp;gt;12 weeks) pregnancy loss in overweight group (BMI≥24 kg/m2) compared to normal group (BMI&amp;lt;24 kg/m2). Main results and the role of chance From 3213 PCOS women conceived after IVF-ET treatment, 1715 (53.4%) women were in overweight group and 1498 (46.6%) in normal group. Baseline characteristics age, primary infertility, pregnancy loss history, endometrial thickness, numbers and types of embryo transferred were not different between two groups. Overweight women had higher serum basal total testosterone and androstenedione levels. Early pregnancy loss (EPL) occurred in 24.2% (415) of overweight women with PCOS versus 21.6% (323) of those with normal weight (OR 1.16, 95% CI 0.98–1.37, P = 0.08). Rates of ELP were also comparable in both groups stratified by age. Overweight women had higher rates of late pregnancy loss (LPL) (6.6% in overweight group versus 3.3% in normal group, OR 2.11, 95% CI 1.50–3.00, P &amp;lt; 0.001). In subgroup analyses, young and advanced-age women with PCOS both had increased chances of LPL with elevated BMI. Logistic regression showed BMI was an independent risk factor of LPL considering age, androgen level, history of previous pregnancy loss, and infertility type. Limitations, reasons for caution Due to the retrospective study, records about gestation-related disease history and smoking were not complete and not shown. However, all patients with IVF-ET were asked to control gestation-related conditions suitable for pregnancy. Proportion of smoking was low and women who planned to conceive were advised to stop smoking before treatment. Wider implications of the findings This study enables physicians to counsel PCOS women undergoing IVF their risk of pregnancy loss more accurately based on personal characteristics. Trial registration number not applicable

P-631 Extended letrozole regimen versus routine letrozole regimen in women with polycystic ovary syndrome undergoing their first ovulation induction cycle

Abstract Study question Whether an extended letrozole regimen could result in a higher ovulatory rate than a routine regimen in PCOS women undergoing their first ovulation induction cycle. Summary answer PCOS women using the extended letrozole regimen failed to obtain a statistically higher rate of ovulation in comparison with the routine letrozole regimen. What is known already Letrozole has become the first-line agent for ovulation induction, however, nonresponsive cycles occurred in 10-58.8% of PCOS women during their ovulation induction therapy with letrozole alone. The extended letrozole regimen has been demonstrated to be a feasible method for inducing ovulation in those nonresponders. However, whether it could be applied to all the PCOS women as a first choice in the induction of ovulation remains to be explored. Study design, size, duration This is a prospective randomized controlled trial including 148 women with PCOS undergoing their first ovulation induction cycle with letrozole from January 2021 to October 2022. Participants/materials, setting, methods Participants were randomly assigned to receive an extended letrozole regimen (5 mg letrozole daily for 7 days) or a routine regimen(5 mg letrozole daily for 5 days) for one treatment cycle. Ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, the rate of multiple pregnancies. Main results and the role of chance The ovulation rate among women receiving a 7-day regimen was slightly higher than the rate with a 5-day regimen, but it did not reach a statistical significance in both the intention-to-treat analysis (90.54%[67/74]vs. 82.43%[59/74], P = 0.065) and per-protocol analysis (90.54%[67/74]vs. 84.29%[59/70], P = 0.257). 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. In the per-protocol analysis, the rates of clinical pregnancy (20.27%[15/74]vs.16.95%[10/70], P = 0.343) and live birth (13.51%[10/74]vs.11.43%[8/70], P = 0.976) did not differ significantly between treatment groups. Moreover, all the conceptions were singletons without neonatal defects. Limitations, reasons for caution The major concern of the current research is its single-centre and open label nature. Additionally, the limited number of lean PCOS women with a mean body mass index of 23-25 kg/m2 enrolled in our trial also restrict the generalizability of our findings. Wider implications of the findings Letrozole 5-day regimen remains to be the first choice for PCOS women undergoing ovulation induction therapy. Additional prospective trials with a larger sample size and different subgroups of PCOS are needed to assess the ovulatory effects of different letrozole treatment duration. Trial registration number ChiCTR2100042082

P-687 High anti-müllerian hormone is associated with lower live birth rate in IVF/ICSI cycle with fresh transfer but not cumulative live birth rate in PCOS women

Abstract Study question Can serum AMH levels affect pregnancy outcomes particularly live birth rate (LBR) and cumulative live birth rate (CLBR) in PCOS women receiving IVF/ICSI treatment? Summary answer Higher serum AMH indicated a decreased LBR and increased miscarriage rate in PCOS women undergoing IVF/ICSI cycle. However, AMH has no association with CLBR. What is known already AMH could reduce follicle sensitivity to FSH and acts as an inhibitor of primordial follicle recruitment, which is essential for follicle growth. Therefore, AMH has widely been suggested to reflect ovarian reserve and predict ovarian response to assisted reproductive technology (ART). Women with PCOS presented AMH level around 2 to 4-fold higher than normal female. The pathological mechanisms of PCOS are complex. Ovarian follicular arrest is regarded as an important pathophysiology of PCOS, which is a consequence of insufficient FSH secretion or inhibition FSH action. Consequently, increased AMH arise might be associated with severity and poor pregnancy outcomes of PCOS. Study design, size, duration This was a retrospective cohort study included 4719 PCOS patients undergoing IVF/ICSI treatment at the Reproductive Center of Peking University Third Hospital from February 2017 to January 2022. Participants/materials, setting, methods Participants were divided into three groups according to the cutoffs defined by the 25th and 75th percentiles of serum baseline AMH level, low-AMH group, n = 1198 (AMH ≤ 4.98 ng/mL); average-AMH group, n = 2346 (4.98 &amp;lt; AMH &amp;lt; 10.65 ng/mL); high-AMH group, n = 1175 (AMH ≥ 10.65 ng/mL). Baseline parameters and pregnancy outcomes including clinical pregnancy rate (CPR), miscarriage rate, LBR and CLBR were compared among three groups. Main results and the role of chance In our cohort, we observed a significant progressively increase in the number of oocytes retrieved and the number of good-quality embryos per cycle from low- to average- to high-AMH group. No statistical significance was observed in fertilization rate (62% vs 60% vs 60%, P = 0.453). In addition, there was no significant difference in CPR among three groups (44.8% vs 42.8% vs 36.8%, P = 0.069). The miscarriage rate was progressively increased from low, average, and high AMH group (11.2% vs 18.5% vs 20.0%, P = 0.023). Importantly, LBR in fresh transfer was progressively decreased from low, average, and high-AMH group (39.6% vs 33.9% vs 29.0%, P = 0.004). However, no statistical difference but an increasing trend was observed in the CLBR among three groups (55.2% vs 56.9% vs 58.1%, P = 0.753). After adjusting by logistic regression analysis, the results indicated that elevated AMH was still strongly associated with decreased LBR in fresh transfer. In addition, BMI, endometrial thickness, and fertilization rate also have correlations with LBR. Nevertheless, the positive relationship between AMH and miscarriage rate remained only in low and average AMH group. Finally, no significant association was shown between AMH and CLBR in logistic regression analysis. Limitations, reasons for caution Firstly, this was a single-center study and might result in bias. Another limitation was due to its retrospective and non-randomized design. Besides, our study indicated an increasing trend in CLBR without statistical significance. Therefore, further large-scale, high-quality prospective cohort studies are still needed to confirm these findings. Wider implications of the findings These findings bring into consideration the potential role of AMH as the guidance in clinical regime. Since high AMH level might act as a biomarker in predicting worse pregnancy outcomes of PCOS women with IVF/ICSI fresh cycle. Trial registration number not applicable

P-609 Impact of low versus air oxygen tension on the oocyte maturation in PCOS women undergoing capacitation IVM: a sibling oocyte pilot study

Abstract Study question Does low or air oxygen tension improve the oocyte maturation rate in biphasic capacitation IVM (CAPA-IVM)? Summary answer Low oxygen tension resulted in a lower maturation rate and two-pronuclei fertilization rate compared with air oxygen tension in the CAPA-IVM culture. What is known already CAPA-IVM, with a pre-maturation step, improves the competence of oocytes matured in-vitro. The current CAPA-IVM culture condition is under air oxygen concentration. However, the impact of oxygen tension on in-vitro oocyte maturation needs to be better understood, and it remains uncertain whether the maturation process aligns with in-vivo conditions. Study design, size, duration A sibling oocyte pilot study of 416 cumulus-oocyte complexes (COCs) recruited from fifteen polycystic ovary syndrome (PCOS) women was performed at IVFMD, My Duc Phu Nhuan Hospital, Ho Chi Minh City, Vietnam from November 2023 to January 2024. The study was approved by the Institutional Ethics Committee (22/23/DD-BVMD, dated October 12th, 2023) and conducted according to Good Clinical Practice and Declaration of Helsinki 2002 principles. All participants provided written informed consent. Participants/materials, setting, methods Women (18–37 years) diagnosed with PCOS undergoing CAPA-IVM were recruited. At collection, COCs from each woman were divided into two groups based on the oxygen tension used in the two steps of CAPA-IVM culture, low oxygen tension (5% O2, 6% CO2 at 37 °C) and air oxygen tension (20% O2, 6% CO2 at 37 °C). Embryos were cultured to blastocyst stage. Primary outcome was the oocyte maturation rate. Secondary outcomes were embryology outcomes. Main results and the role of chance A total of 416 COCs from fifteen eligible women were assigned to the low oxygen (207 COCs) and air oxygen tension (209 COCs) groups. Mean age and body max index were 29.0±2.5 years and 22.6±2.6, respectively. The maturation rate was significantly lower in the low oxygen group compared to the air oxygen group (54.1% vs. 66.5%, p = 0.01, respectively). The two-pronuclei fertilization rate per COC was significantly decreased in the low oxygen group compared to the air oxygen group (35.7% vs. 49.3%, p = 0.005, respectively). Rates of day-3 embryos, blastocyst formation rate, and good quality blastocyst rate were also lower but not significant in the low oxygen tension group as compared to the air oxygen tension group. Limitations, reasons for caution The study’s limitations include a relatively small sample size and a single ethnicity group. There was a lack of data on clinical outcomes after transferring embryos from the study. Wider implications of the findings Oocyte maturation rate and two-pronuclei fertilization rate were significantly lower when oxygen tension was reduced in the process of CAPA-IVM culture. Therefore, air oxygen tension should be considered as a standard for oocyte culture in the pre-maturation step of CAPA-IVM. Trial registration number NCT06087354

O-257 Comparing the accuracy of the novel clustering model versus phenotype classification in predicting live birth in polycystic ovary syndrome women undergoing In-Vitro fertilization

Abstract Study question Is the clustering model more accurate than phenotype classification in predicting live birth in polycystic ovary syndrome (PCOS) women undergoing in vitro fertilization (IVF)? Summary answer Novel PCOS clusters, identified by patients’ endocrine and metabolic profiles, more accurately predict live birth rates in women undergoing IVF than the traditional phenotype classification What is known already PCOS is a heterogeneous condition that affects fertility and IVF success. It is classified based on three factors: hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovaries (PCOM). The ESHRE/ASRM classification system identifies four phenotypes: A (including all three factors), B (HA and OD), C (HA and PCOM), and D (OD and PCOM). Although this classification is widely used, its focus solely on clinical signs and symptoms, while neglecting underlying endocrine and metabolic factors, may limit its effectiveness in predicting fertility outcomes in PCOS patients. Therefore, classifying PCOS patients may require a more comprehensive and inclusive assessment approach. Study design, size, duration This prospective cohort study was conducted from June 2020 to August 2022 at a tertiary IVF center in Ho Chi Minh City, Vietnam. Clustering models were built based on the endocrine and metabolic profiles of 731 PCOS patients. Patients were grouped into novel clusters based on their endocrine and metabolic profiles and compared with traditional phenotypes classification. The primary outcome measured was the live birth rate. Participants/materials, setting, methods Patients aged 18–45, diagnosed with PCOS according to the Rotterdam 2003 criteria, and undergoing IVF treatment were included in the study. Patients with hypothyroidism, Cushing’s syndrome, congenital adrenal hyperplasia, or contraindications to hormonal treatment were excluded. We employed Gaussian Mixture Models for clustering, using endocrine and metabolic data as the key features. We then compared the accuracy of the clustering model with phenotype classification in predicting IVF outcomes using a logistic regression model. Main results and the role of chance We identified three distinct clusters among polycystic ovary syndrome (PCOS) patients. Cluster 0 (n = 298) was characterized by significant insulin resistance and dyslipidemia. Cluster 1 (n = 219) displayed the lean PCOS phenotype, and Cluster 2 (n = 214) had moderate insulin resistance with severe hyperandrogenism. Our findings indicated that Clusters 1 and 2 had a higher cumulative live birth rate (CLBR) (39.7% and 37.9% versus 28.5% in Cluster 0, p = 0.015) and lower gestational diabetes rates (8.68% and 6.07%, respectively) compared to Cluster 0 (12.4%, p = 0.048). Additionally, the prevalence of hypertensive disorders during pregnancy showed differences across clusters (3.69% in Cluster 1, 0.46% in Cluster 2, and 2.8% in Cluster 0, p = 0.059). In contrast, the traditional phenotype classification did not demonstrate significant differences in CLBR, gestational diabetes, and hypertensive disorders. The cluster-based method provided a more accurate prediction of CLBR using logistic regression, with an AUC of 0.67 (95% CI: 0.57-0.76) compared to 0.49 (95% CI: 0.41-0.59) for traditional classifications (p = 0.001) Limitations, reasons for caution This is a single-center study conducted on Vietnamese patients. Therefore, the generalizability may be limited. The novel clustering’s predictive value for IVF outcomes in PCOS patients requires further validation in prospective studies. Wider implications of the findings This study suggests a potential shift towards personalized IVF treatment strategies for PCOS, using machine learning-based PCOS clustering identified by patients’ endocrine and metabolic profiles. Trial registration number NCT04364087

P-698 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using May Health System in women with PCOS-related infertility: clinical and endocrine outcomes of first–in-human feasibility trial

Abstract Study question What is the feasibility of transvaginal ULTRAsound (TVUS)-guided ovarian ablation using the May Health System to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related infertility? Summary answer The feasibility of TVUS-guided ovarian ablation to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related anovulatory infertility was demonstrated. A pivotal study is underway. What is known already Laparoscopic ovarian drilling (LOD) is widely accepted as an effective second line treatment in PCOS-related infertility. However, laparoscopy is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, there is no standardization of the LOD technique among surgeons. In contrast, the May Health System has been designed to deliver a precisely calculated amount of ovarian ablation via a less invasive route without general anaesthesia. This approach therefore transforms an invasive surgical procedure to an office-based technique similar in ovarian access to the well-established oocyte retrieval. Feasibility and safety results of this trial have previously been reported. Study design, size, duration This study included two feasibility, single-arm clinical trials running in parallel in the EU and US assessing the May Health System in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was up to 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints for this study were technical success, ovulation rates, pregnancy rates, and hormonal changes. Participants/materials, setting, methods Seven fertility centres participated in the trials. Participants were clomiphene/letrozole-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using the May Health System. The initial five participants underwent laparoscopy concurrent with TVUS-ablation. Post-procedure, serum progesterone was measured weekly until confirmation of ovulation or up to 12 weeks. Women were evaluated at 3 and 6 month, and then telephoned at 9- 12- and 24-month (EU sites only). Main results and the role of chance Thirty-one participants (mean±sd age, 31.9±3.3 years; BMI, 29.84.7kg/m2) underwent May Health TVUS-guided ovarian ablation and 25 completed at least six-months FU, with follow-up ongoing. Fourteen (45.2%) ovulated spontaneously within 3-months. Six more participants (19.3%) ovulated between three and nine months (after restarting CC/LTZ) giving a combined ovulation rate, with and without first-line medication restart, of 64.5% (20/31). Of the 31 participants who underwent the procedure, 10 (32%) have conceived to date, with seven live births, two ongoing, and one miscarriage. In 30 cases (97%), the targeted ablation was achieved successfully, while in one case (3%) the procedure was abandoned for the second ovary due to pain (n = 1). The median (IQR) serum AMH concentrations significantly decreased from baseline 76.1 (32.0, 210.7) to 62.5 (21.2, 253.6) pmol/l at 3-month (p = 0.001) and 56.7 (11.5, 126.8) pmol/l at 6-month (p = 0.001) post-procedure (Figure 2). The magnitude of post-ablation AMH decline was significantly (p = 0.047) greater in those who ovulated (responders) (-23.7% (-36.5, 17.7)) versus non-responders (-7.3% (-25.2, -1.6)). Ovarian volume significantly (p = 0.005) decreased from 13.6±5.1 ml at baseline to 10.1±3.7 ml at 6-month FU. There were no statistically significant changes in mean circulating testosterone, LH, or FAI at 3- or 6-month. Limitations, reasons for caution A limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility trial. It is possible to assume that the post-procedure ovulation and pregnancies could be compared for each participant with pre-procedure lack of ovulation and failure to conceive. Wider implications of the findings These data suggest that the investigational May Health System may offer an effective office-based second line ovulation inducing procedure for PCOS. The observed decline in circulating AMH, which was sustained for at least six months, could be the underlying mechanism of ovarian rebalancing that leads to subsequent resumption of ovulation. Trial registration number NCT03760926

P-604 Underlying molecular mechanisms of Polycystic Ovary Syndrome and Morphology: focusing on the ovary

Abstract Study question What mechanisms are involved in the ovarian alterations of Polycystic Ovary Syndrome (PCOS) and Morphology? Summary answer PCOS patients associated a distinctive impairment of oxidative phosphorylation and dysregulated complement system in their follicular compartments not found in Polycystic Ovarian Morphology (PCOM) women. What is known already PCOS is a major cause of female infertility characterized by aberrant follicular development and hormonal imbalances leading to reproductive symptoms such as anovulation, poor oocyte quality, and hyperandrogenism. Likewise, PCOM is present in 16-25% of women with regular menses, but the clinical relevance of this ovarian phenotype and its correlation with PCOS remains unclear. Therefore, to establish the specific molecular mechanisms underlying the ovarian alterations in PCOS using High-throughput techniques will allow us to provide a better clinical management and a differential diagnosis with PCOM women. Study design, size, duration Cross-sectional molecular study including samples from 26 patients undergoing an IVF cycle between 2019-2022 at Hospital La Fe (Valencia, Spain). Eight women were considered PCOS, eleven PCOM and seven were control fertile patients. Granulosa cells (GCs) and follicular fluid (FF) samples were obtained during oocyte retrieval to perform RNA-seq and proteomic analysis, respectively. Participants/materials, setting, methods Women with two or more Rotterdam-criteria were considered as PCOS, while PCOM was defined by polycystic ovarian morphology on ultrasound with regular ovulatory cycles. RNA from GCs was obtained and sequenced using NextSeq500-Illumina to identify differentially expressed genes (DEGs) using DESeq2 (R-software). The proteome of FF samples was established by LC-MS/MS and differentially expressed proteins (DEPs) analyzed with limma package. Functional enrichment analysis of DEGs and DEPs (FDR&amp;lt; 0.05) was performed based on KEGG database. Main results and the role of chance RNA-seq data revealed clear distinctions between GCs from PCOS and control women, with 526 DEGs. By contrast, the transcriptomes of PCOS and PCOM were more similar, with only 34 DEGs. Notably, oxidative phosphorylation emerged as the most enriched pathway in both comparisons, showing a differential expression in PCOS. Indeed, 6 out of 12 shared DEGs (MT-TP, MT-ND4L, MT-ND2, MT-ATP8, MT-ND4, and MT-ATP6), were mitochondrial genes found upregulated in PCOS vs. PCOM and control samples. These findings suggest that granulosa cells from PCOS present a dysregulation in oxidative phosphorylation, potentially linked to alterations in those genes associated with the mitochondrial electron transport chain. The proteomic analysis showed 37 DEPs in the FF of PCOS compared with controls, being these DEPs mainly involved in the complement and coagulation cascades, PI3K-AKT pathway, oocyte meiosis and ferroptosis. Furthermore, the PCOS vs. PCOM analysis revealed 42 DEPs, significantly enriched also in complement and coagulation cascades, ferroptosis and glutathione metabolism. Interestingly, fifteen proteins were differentially expressed in both comparisons, with four of them related to the complement system (PROS1, C1S, C1QB and MASP2), suggesting that an alteration in this system at follicular fluid level might be one of the hallmarks of PCOS. Limitations, reasons for caution Further experimental studies are required to validate the specific changes identified in our study. Moreover, to establish how these alterations in the follicular compartments affect the oocytes of PCOS patients should also be explored. Wider implications of the findings Our study focused on specific mechanisms involved in PCOS ovarian alterations, providing new insights into potential biomarkers for an accurate diagnosis and management of this pathology. Dysregulations in oxidative phosphorylation and complement system might play a crucial role in PCOS multifactorial nature, contributing to impaired folliculogenesis and decreased oocyte quality. Trial registration number Not Applicable