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PubMed2006

Treatment of PCOS in adolescence.

Polycystic ovary syndrome (PCOS) is increasingly being recognized in adolescent girls seeking treatment for signs and symptoms of hyperandrogenism. It is difficult to diagnose PCOS in adolescents, therefore a high index of suspicion is necessary. Timely screening and treatment are crucial because another important component of the syndrome is insulin resistance/hyperinsulinemia increasing the risk for type 2 diabetes, dyslipidemia, and cardiovascular sequelae. Diagnosis of PCOS in adolescents should include a thorough family history, exclusion of other causes of hyperandrogenism, and appropriate laboratory evaluation. The scarcity of controlled clinical trials makes treatment controversial. Therapeutic options include lifestyle intervention, oral contraceptive pills, and insulin sensitizers. Long-term follow-up is needed to determine the effectiveness of these approaches in changing the natural history of the reproductive and metabolic outcomes without causing undue harm.

Adolescent↗

PubMed2005

Transabdominal pulse inversion harmonic imaging improves assessment of ovarian morphology in virgin patients with PCOS: comparison with conventional B-mode sonography.

OBJECTIVE: In virgin policystic ovary syndrome (PCOS) patients transabdominal sonography is the preferential method of the pelvic examination. The purpose of this study was to determine ovarian morphology by the transabdominal route by pulse inversion harmonic imaging (PIHI) in virgin PCOS patients and to compare the diagnostic image quality with conventional B-mode ultrasonography (CBU). METHODS: Fifty-two ovaries in 26 virgin patients were evaluated by the transabdominal approach. Each ovary was examined using both PIHI and CBU. The sharpness of the follicular cysts walls, degree of internal echo definitions of the follicle cysts and overall ovarian conspicuity was assessed subjectively, using 4 point scoring (0, being worst; 3, being best score). The number of countable follicles, the size of largest and smallest ovarian follicle and ovarian volumes were assessed quantitively by both techniques. The effect of body mass index (BMI) on qualitative and quantitative scoring was evaluated. RESULTS: The sharpness of the cyst wall and internal echo structure was significantly better with PIHI than with CBU (P < 0.001 P < 0.001 and P < 0.001, respectively). PIHI improved overall ovarian conspicuity in 41 (78.8%) of 52 examination. The number of countable follicles was significantly lower with CBU (P < 0.001). The maximum diameter of the largest follicle was larger with PIHI sonography to compared CBU (P < 0.001). Mean ovarian volume was significantly larger with CBU (P < 0.001). When data were analyzed separately according to BMI, number of non-diagnostic overall ovarian conspicuity scores with CBU was markedly high in obese patients (88% with CBU versus 3.8% with PIHI). On the other hand, mean number of countable follicles with CBU became much more lower in the obese group (P < 0.001). CONCLUSION: In virgin PCOS patients, when compared to transabdominal CBU, PIHI significantly improved the detection of ovarian follicles, especially in high BMI obese subjects, through increased contrast sensitivity for cystic structures and decreased intrafollicular artifactual echoes. Transabdominal ultrasonographic examination by PIHI mode can contribute to the evaluation of ovaries.

Adolescent↗

PubMed2001

Improved responsiveness of PCOS patients to clomiphene after CYP17a inhibitor.

PURPOSE: To study the effect of CYP17a inhibitor, "ketoconazole," on clomiphene responsiveness in PCOS patients. METHODS: Prospective analysis was employed with the setup at Alexandria IVF/ICSI center. Ninety-seven insulin-resistant PCOS patients undergoing ovulation induction using clomiphene citrate were randomly divided, by random number table, into two groups. The first group (n = 49) received ketoconazole (400 mg daily) till correction of metabolic syndrome followed by clomiphene (100 mg/day); the second group (n = 48) receiving clomiphene without ketoconazole pretreatment. Main outcome measures were incidence of clomiphene resistance, monofollicular response, fasting insulin/glucose ratio, serum testosterone, and pregnancy rates. RESULTS: The ketoconazole group showed significantly (p < 0.05) higher incidence of monofollicular response (38%), higher pregnancy rates, and significantly less marked antiestrogenic manifestations than did the control group. They also had significantly lower incidence of clomiphene resistance (11.6%), lower serum testosterone levels, less hyperinsulinaemia, than did the control group. CONCLUSION: Ketoconazole improved clomiphene responsivenss in PCOS patients and attenuated its untoward biological effects.

Clomiphene↗

PubMed2004

Serum leptin elevation in obese women with PCOs: a continuing controversy.

PURPOSE: To evaluate leptin levels in a sample of obese women with PCOS and compare the results with obese and non-obese control, to be ultimately correlated with BMI, and insulin sensitivity. METHODS: Leptin and insulin assays by immuno-radiometric method, glucose assay by enzymatic colorimetric method. RESULTS: Leptin levels were significantly different between obese and non-obese subjects, and were significantly different between insulin resistant and non-insulin resistant obese PCOS, but were not significantly different between obese non-insulin resistant PCOS, and obese controls. CONCLUSIONS: Body mass index and insulin resistance are the two main factors governing serum leptin levels.

Adult↗

PubMed2001

Basal and day 12 inhibin concentrations in the prediction of ovarian response to gonadotrophins in women with PCOS.

BACKGROUND: In this study, we aimed to investigate whether basal and day 12 serum total inhibin concentrations in women with polycystic ovarian syndrome (PCOS) were of predictive value for the estimation of the ovarian response to gonadotrophins. METHODS: Ovulation induction with a very low dose gonadotrophin protocol, starting with 37.5 IU/day, was performed for 40 cycles on 35 patients with PCOS. Day 3 (basal) serum total inhibin, FSH and oestradiol concentrations; day 12 dominant follicle diameter, inhibin and oestradiol concentrations and midluteal serum progesterone concentrations were measured during the 40 cycles. The correlations between basal and day 12 inhibin concentrations and some critical ovulation monitoring parameters were investigated. RESULTS: Ovulation was obtained in 14 out of 40 cycles: 21% of cycles with basal inhibin <1.0 IU/ml; 33.3% of cycles with basal inhibin between 1.0-1.9 IU/ml; and 83.3% of those with inhibin concentrations > or =2 IU/ml were ovulatory (P < 0.05). Ovulation was achieved in 91.6% of the cycles with a day 12 inhibin concentration > or =4 IU/ml. CONCLUSIONS: Basal inhibin concentrations may determine poor and good responders to ovulation induction with very low dose gonadotrophin protocol in patients with PCOS. The day 12 inhibin concentration was found to be a more sensitive parameter than the oestradiol concentration in the prediction of follicular maturation.

Adult↗

PubMed2002

Blastocyst development and pregnancies after IVF of mature oocytes retrieved from unstimulated patients with PCOS after in-vivo HCG priming.

A major side-effect of controlled ovarian stimulation (COS) in patients with polycystic ovarian syndrome (PCOS) is the risk of ovarian hyperstimulation syndrome (OHSS). In-vitro maturation (IVM) of immature oocytes represents a potential alternative for the fertility treatment of these patients. Two patients at high risk of OHSS were primed with 10,000 IU HCG 36 h before oocyte retrieval. After retrieval, oocyte maturity was evaluated. Oocytes considered to be mature at the time of collection were inseminated by IVF or ICSI, and the resulting embryos were cultured to blastocysts. Transfer of these blastocysts resulted in pregnancy in both patients. Immature oocytes were cultured in YS medium supplemented with 30% human follicular fluid, 1 IU/ml rFSH, 10 IU/ml HCG and 10 ng/ml epidermal growth factor (rhEGF). After in-vitro maturation of the oocytes, ICSI was performed. Two and five expanded blastocysts were obtained after 5 day culture and were cryopreserved. This report indicates that mature oocytes can be collected at the time of retrieval using only in-vivo HCG priming in women with PCOS, and clinical pregnancy can be established by transfer of blastocysts derived from the mature oocytes. This approach opens a potential for a new dimension in the management of patients with PCOS.

Adult↗

PubMed2006

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study.

BACKGROUND: The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). METHODS: A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. RESULTS: Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). CONCLUSION: Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.

17-alpha-Hydroxyprogesterone↗

PubMed1992

Investigation of adrenal function in women with oligomenorrhoea and hirsutism (clinical PCOS) from the north-east of England using an adrenal stimulation test.

OBJECTIVE: To determine the prevalence of adrenal enzyme dysfunction in women presenting with oligomenorrhoea and hirsutism, two clinical features of polycystic ovary syndrome (PCOS). DESIGN: A prospective study of women attending outpatient clinics with these complaints. Androstenedione, dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol and cortisol were measured before and after overnight dexamethasone suppression and at 60 minutes after adrenal stimulation by ACTH injection. SUBJECTS: Fifty women with clinical features of PCOS and 37 control women with regular cycles and normal hair distribution from the catchment area of the Royal Victoria Infirmary which includes Newcastle upon Tyne, Co. Durham, Cleveland, Cumbria and Northumberland. MEASUREMENTS: Number of women with steroid responses to ACTH beyond the normal range, as defined by the responses of the control group and in previous studies. RESULTS: Nineteen women (38%) were found to have some abnormality. One woman (2%) was identified with 21-hydroxylase (21-OHase) deficiency and a second (2%) had an increase in 17-OHP compatible with the heterozygote state for 21-OHase deficiency. Four women (8%) had isolated elevations in the DHEA response consistent with minimal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency. Thirteen women (26%) showed increases in both androstenedione and DHEA, or androstenedione alone, compatible with enhanced 17-20 lyase activity. CONCLUSIONS: Twelve per cent of the group showed evidence consistent with an adrenal enzyme deficiency; 26% had results in keeping with increased adrenal androgen production without an enzyme deficiency. These findings may be of relevance both in the pathogenesis of the features of PCOS and in determining appropriate treatment for individual patients.

3-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Octreotide effect on ovarian morphology in insulin-resistant PCOS patients following six-month decapeptyl treatment.

PROBLEM: Regulation of ovarian folliculogenesis involves bidirectional communication between the immune and endocrine systems. Somatostatin analogues have been reported to acutely suppress elevated androgens in polycystic ovary syndrome (PCOS). The aim of our study was to analyze the morphologic and hormonal-metabolic response to octreotide therapy for one month in insulin-resistant PCOS patients in whom luteinizing hormone (LH) effect had formerly been separated by a six-month GnRH-agonist (GnRH-a) course. METHOD: Fifteen PCOS patients were studied two months after completing a six-month GnRH-a (decapeptyl 3.75 mg monthly injection) course. Seven of the patients (group A), who were insulin-resistant and gave hyperinsulinemic response to a glucose challenge, received a 50-micrograms subcutaneous injection of octreotide twice a day for one month. The nonhyperinsulinemic patients (group B) received placebo injections. Hormonal measurements, oral glucose tolerance test (OGTT), and transvaginal ovarian ultrasound were performed before and toward the end of the treatment period. RESULTS: After octreotide ovarian volume dropped significantly in group A (x +/- SD) (19.2 +/- 5.1 versus 14.7 +/- 5.5 cc, P = .02). LH levels increased (3.25 +/- 1.22 versus 5.95 +/- 4.34 mu/ml, P = .05) as did E2 levels (38.0 +/- 11.4 versus 55.1 +/- 12.7 pg/ml, P = .005). There was no change in follicle-stimulating hormone, 17-hydroxy-progesterone, free testosterone, or androstenedione levels. Insulin secretion during OGTT dropped significantly (555 +/- 294 versus 68 +/- 29 mu u/ml/hr, P = .002). Glucose tolerance was not affected. In contrast, the placebo-treated group B patients showed an increase in ovarian volume (10.9 +/- 3.5 versus 14.8 +/- 3.3 cc, P = .001) while their gonadotropin and steroid profile relapsed, similarly to our patients receiving octreotide. CONCLUSIONS: Octreotide has an adjunctive beneficial effect to GnRH-a on ovarian morphology although, at the dose used, there was no suppression of gonadotropin or ovarian steroid levels. The changes in ovarian morphology are probably mediated through suppression of insulin levels and/or other ovarian growth factors.

Adolescent↗

PubMed2003

Effect of two modes of antiandrogen treatment on insulin sensitivity and serum leptin in women with PCOS.

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Adipose Tissue↗

PubMed1996

Laparoscopic ovarian treatment in infertile patients with polycystic ovarian syndrome (PCOS): endocrine changes and clinical outcome.

During the years 1991-1994, 97 anovulatory infertile women with polycystic ovarian syndrome (PCOS) were treated with laparoscopic electrocautery of the ovarian surface after they had failed to ovulate under ovarian stimulation. To assess the endocrinological and clinical outcome and in an attempt to determine the mechanism of action, the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were determined before and after laparoscopic ovarian cautery. Fifty regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with PCOS but not in controls, the reduction of androgen levels and normalization of cycle length were highly significant. In contrast, LH and FSH levels rose during the first 2 days after the operation. These results resemble those reported after ovarian wedge resection. Ovulation was obtained in 90% (81 of 90) and pregnancy in 81.1% (73 of 90) of the patients; that increased to 84.4%, including the non-responders (nine patients) treated with clomiphene citrate (CC), after electrocautery. The response to ovarian electrocautery was influenced by body weight, with an ovulation rate of 95-96% in the slim and moderately obese women, decreasing to 81-82% in the really obese ones. When ovulation was established, the pregnancy rate was independent of body weight. However, a striking relationship was detected between smoking habits and pregnancy rate subsequent to ovarian electrocautery, ranging from 24% in smokers to 92% in non-smoking couples. In 30 second-look operations, de novo adhesions were found in 23.3% of the patients (7 of 30). Therefore, ovarian electrocautery is an effective procedure to improve the intraovarian mechanism of selecting a dominant follicle for patients with PCOS in whom initial medical management fails, and it appears to be one of the possible treatments for this disease. A possible postoperative complication may be adhesion formation that seem to be lower than after ovarian wedge resection.

Adult↗

PubMed1999

Endometrial fluid collection in women with PCOS undergoing ovarian stimulation for IVF. A report of four cases.

BACKGROUND: The presence of endometrial fluid collections' developing during ovarian-stimulation was previously reported to occur in women with hydrosalpinx. We report on the occurrence of endometrial fluid collections in four women with polycystic ovary syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization. CASES: Four women developed endometrial fluid collections during ovarian stimulation. These fluid collections were noted as early as day 5 of stimulation. The reproductive outcome when fluid collections were noted on the day of human chorionic gonadotropin (hCG) or of embryo transfer (ET) was poor. One of three women with fluid collection on the day of hCG conceived but had a missed abortion. One patient with fluid on the day of ET failed to conceive. Three of four patients who underwent repeat cycles conceived when no fluid collections were seen on day of hCG or ET. CONCLUSION: Abnormal endometrial milieu could be an underlying defect in some women with PCOS and chronic anovulation who fail to conceive with ovulation-induction agents. This is the first report of endometrial fluid collections in patients with PCOS in the absence of hydrosalpinx. Continuous monitoring of the endometrial lining during ovulation induction is mandatory to rule out any abnormality in endometrial development. Cryopreserving all embryos may be considering in cycles with fluid collections noted on the day hCG or ET.

Adult↗

PubMed1999

[The use of the preparation Anteovin in dysfunctional uterine hemorrhages and PCOS].

UNLABELLED: The present prospective study is aimed at estimating the therapeutic effect of a biphasic oestrogen dominated contraceptive pill Anteovin in certain forms of dysfunctional uterine bleeding (DUB) and in polycystic ovary syndrome (PCOS) which is associated with dysfunctional bleeding. Two groups of women were studied--the first group (n = 34) consisted of women with DUB; the second group (n = 31) comprised PCOS. The nature and dynamics of uterine bleeding, contraceptive effectiveness and occurrence of side effects were followed up. In the second group the changes in the levels of testosterone (T), dehydroepiandrosterone sulfate (DHEA-S) and prolactin (Prl) were additionally investigated. RESULTS: A significant decrease in bleeding was observed in both groups. In the second group it is in parallel with a significant decrease of T even as early as on the third month and of DHEA-S on the sixth month of treatment. No significant changes in prolactin levels were found out during the treatment. CONCLUSION: The biphasic contraceptive pill Anteovin has a very good therapeutic effect in DUB and metrorrhagic forms of PCOS while at the same time the side effects are slightly expressed and transitory and an excellent contraception is achieved.

Adolescent↗

PubMed2000

[Comparison of conservative and laparoscopic treatment of PCOS].

OBJECTIVE: Aim of study contained clinical analysis of results conservative (Clostilbegyt) and laparoscopic (electro-catheterisation of ovaries) methods of treatment PCOS. Authors analysed count of pregnancy, deliveries and serum concentrations of LH, FSH, LH/FSH ratio, 17 beta E2 before and after treatment. MATERIAL AND METHODS: Stady included 50 obese patients (group A, BMI > 28) treated by Clostilbegyt and 50 lean patients (group B, BMI < 28) treated by laparoscopic ovarian electrocautery. RESULTS: We found higher percentage of pregnancies (84%) and deliveries in group B (72%) versus A. We obtained statistically significant higher serum concentrations of LH, 17 beta E2 and LH/FSH ratio of group B versus A. CONCLUSIONS: 1. Recommendation method for treatment PCOS is a laparoscopic electro-catheterisation of ovaries. 2. This method stabilize hormonal secretion of hypothalamic-pituitary-ovarian axis in the PCOS.

Adult↗

PubMed2000

Multiple ovarian biopsy in the treatment of women with polycystic ovary syndrome (PCOS).

BACKGROUND: Ovarian electrocautery has been used with success in the treatment of PCOS women. However, unipolar coagulation carries the risk of serious injuries to pelvic organs. In an effort to avoid this potential risk, the efficacy of multiple ovarian biopsy was evaluated in our study. METHODS: Eleven PCOS patients were enrolled to the study. Four to eight biopsies were taken from both ovaries. The levels of LH, FSH, androgens and the reactivity of ACTH test were evaluated at standard intervals. The occurrence of ovulation was determined by ultrasound. RESULTS: Laparoscopy was followed by non-significant changes of endocrine parameters only. The ovulatory cycle was restored in only three women of the whole group. CONCLUSIONS: Our study did not prove the efficacy of multiple ovarian biopsy in the treatment of PCOS women. The procedure caused only minor changes in endocrine parameters and rarely restored ovulation.

17-alpha-Hydroxyprogesterone↗

PubMed1999

Endocrinological and genetic studies in patients with Polycystic Ovary Syndrome (PCOS).

Our studies involved 21 women of Caucasian descent with PCOS, as diagnosed by ultrasound, clinical and hormonal findings. We determined 17alpha-OHP, 21-DOF and cortisol levels both just before and one hour after intravenous ACTH administration (0.25 mg Synacthen) in addition to the basal plasma levels of DHEA-S and free testosterone. We screened the CYP21 gene for 12 common-point mutations, finding five heterozygous mutations in 4 out of 21 cases (19%): a splice-site mutation in intron 2 in three cases, and a I172N mutation in exon 4 in two cases. These patients also displayed significantly higher 21-DOF or 17alpha-OHP plasma levels after ACTH administration, suggesting a partial 21-hydroxylase deficiency. Furthermore, we found the basal plasma DHEA-S levels or DHEA-S/F ratios in 11 of 21 patients (52%) to be higher than the means + 2SD of control females, indicating partial 3beta-HSD deficiency or 17,20-LHA. According to the literature, mutations could not be found in the genes of PCO cases with hormonal activity changes in the last two enzymes. The DDT metabolite o,p'-DDD is a strong inhibitor of 3beta-HSD, and DDT can induce 17,20-LHA, implying a possible connection between cases of PCOS women born in East Germany after 1955 and their prenatal DDT uptake. The approximately fourfold higher prevalence of PCO and significantly increased frequency of 3beta-HSD-deficiency and 17,20-LHA found in women with PCOS born since 1955-the time of massive application of DDT-give weight to the thesis that DDT, rather than genetic factors, has played a part in this upsurge.

Journal Article↗

PubMed2003

[Comparative diagnostic characteristics of carbohydrate metabolism disorders in women with polycystic ovary syndrome (PCOS)].

The aim of the study was to compare the information provided by both fasting and stimulated during a standard oral glucose tolerance test (oGTT) levels of glucose and insulin as regards glucose tolerance and insulin resistance in women with PCOS. Few criteria are used in practice to verify insulin resistance in PCOS--elevated fasting insulin, decreased basal glucose/insulin ratio (< 6 for glucose in mg/dl or < 0.333 for glucose in mmol/l), insulin increase of more than 100 lul during an oGTT, and HOMA index > 2. The study comprised of 94 women (mean age 21.8 +/- 5 = 8 ys, mean BMI-30.38 +/- 7 = 7 kg/m2), divided in 4 groups according to BMI--group with BMI < 25, n = 21; group with BMI25-30, n = 27; group with BMI = 30-35, n = 23 and group with BMI > 35, n = 23. An oGTT with parallel determination of blood glucose and insulin was performed in all patients. The ratio basal glucose/insulin and HOMA index were calculated. Glucose levels on the 2 md hour during the oGTT pointed at IGT (impaired glucose tolerance) and/or diabetes in 8.5% of the investigated patients while the fasting levels indicated disturbances in only 2.2% of them. Fasting insulin levels were in the normal range in a considerable part of PCOSE women, mainly those with normal weight, and were not predictive for the response of insulin to glucose load. Relative percent of patients with elevated fasting insulin rose with the increasing of BMI. Decreased glucose/insulin ratio, elevated HOMA index, and abnormal stimulation of insulin were seen in more than 2/3 of the PCOS women including nonobese ones. Information provided by the above three markers was similar and they could be used alternatively according to the particular case and assessment of the cost/benefit ratio.

Adolescent↗

PubMed2026

Epigenetic safety of in vitro maturation in PCOS: genome-wide DNA methylation profiling of cord blood from a randomized controlled trial.

BACKGROUND: In vitro maturation (IVM) provides a safer alternative to conventional in vitro fertilization (IVF) for women with polycystic ovary syndrome (PCOS) by mitigating the risk of ovarian hyperstimulation. However, concerns persist regarding whether IVM perturbs epigenetic reprogramming in the offspring. Current evidence is constrained by candidate-gene approaches or a lack of parental controls. This study aimed to evaluate the genome-wide DNA methylation safety of IVM compared with conventional IVF using a rigorous trio-based design. METHODS: This secondary epigenetic analysis was nested within a randomized controlled trial (RCT) (ClinicalTrials.gov: NCT03463772). We included 10 nuclear families (trios), comprising five IVM-conceived and five IVF-conceived singleton offspring alongside their biological parents. Both groups utilized a uniform freeze-only single-blastocyst transfer strategy to minimize hormonal confounding. Genomic DNA from umbilical cord blood (UCB) and parental peripheral blood was analyzed using reduced representation bisulfite sequencing (RRBS). Genome-wide methylation patterns and differentially methylated regions (DMRs) were subsequently compared between the groups. RESULTS: Clinical characteristics were comparable between the IVM and IVF groups. Genome-wide analyses demonstrated high concordance in UCB methylation patterns, revealing no significant differences in global CpG methylation levels or distributions across key genomic features (promoters, CpG islands, and gene bodies). Only three rare DMRs were identified in UCB (representing ~ 0.0001% of the genome), none of which mapped to imprinted or developmentally critical loci. Furthermore, methylation variability remained consistent between the groups. CONCLUSIONS: Our findings provide robust mechanistic evidence supporting the epigenetic safety of IVM. The remarkable stability of the neonatal methylome confirms that specific IVM conditions do not compromise early developmental programming, thereby endorsing IVM as a safe and viable alternative for women with PCOS. TRIAL REGISTRATION: ClinicalTrials.gov registry, NCT03463772. Registered on March 13, 2018.

Humans↗