Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes

Controlled ovarian stimulation (COH) in PCOS is a challenge for fertility expert both ovarian hyperstimulation syndrome (OHSS) and oocytes immaturity are the two major complication. Ovarian response to COH vary widely among POCS patients and while some patients are more likely to show resistance to COH, other experienced an exaggerated response. The aim of our study is to investigate a possible correlation between PCOS phenotypes and the variety of ovarian response to COH and ART outcomes in patients with different PCOS phenotypes. We retrospectively analyzed a total of 71 cycles performed in 44 PCOS infertile patients attending ART at Centre of Infertility and Assisted Reproduction of Pisa University between January 2013 and January 2016. Patientsundergoing IVF with GnRH-antagonist protocol and 150–225?UI/days of recombinant FSH; triggering was carried out using 250 mg of recombinant hCG or a GnRH analogous on the basis of the risk to OHSS. We observed that Phenotype B had a tendency to have a greater doses of gonadotropins used respect to all phenotypes. Phenotype A group showed a greater serum estrogen levels compared to all phenotypes groups, a greater number of follicles of diameter between 8–12?mm found by ultrasound on the day of triggering and a greater mean number of freeze embryo. Additionally serum AMH and antral follicles count (AFC) follow the same trend in the different phenotypes ad they were significantly higher in phenotype A and in phenotype D. In conclusion this study shows that the features of PCOS phenotypes reflect the variety of ovarian response to COH as well as the risks to develop OHSS. Serum AMH and AFC are related to the degree of ovulatory dysfunction making these ‘added values’ in identifying the different PCOS phenotypes. Phenotype A seems to be the phenotype with the higher risk to develop OHSS and the use of GnRH as a trigger seems to improve oocyte quality. To classify PCOS phenotype at diagnosis might help clinicians to identify patients at greater risk of OHSS, customize therapy and subsequently plan the trigger agent.     

Metformin treatment in different phenotypes of polycystic ovary syndrome

Background

The aim of this study was to evaluate the effectiveness of Metformin on ovulation and eventual clinical pregnancy in different phenotypes of polycystic ovary syndrome (PCOS).

Materials and methods

A total of 359 subjects who had proven PCOS according to Rotterdam criteria were prospectively selected. Patients’ PCOS phenotypes were determined and recorded. All patients were younger than 35 years. Clinical and biochemical assays in all patients were initially obtained. Then patients were divided into two separate groups. One group received both 1,500 mg of Metformin and 1 mg of folic acid per day and the other group received only 1 mg of folic acid for a total of 2 months. Subsequently, all patients underwent ovulation stimulation with 5 mg of Letrozole per day for 5 days followed by an intra-uterine insemination. Finally, ovulation and pregnancy rates were evaluated for all four PCOS phenotypes. Effect of Metformin therapy was evaluated for each group and each phenotype.

Results

The pregnancy rate in Metformin and non-Metformin groups were, respectively, as follows: in phenotype A (39.2 vs. 33.7 %, p = 0.270), phenotype B (43.8 vs. 20 %, p = 0.210), phenotype C (44 vs. 20 %, p = 0.064), and phenotype D (36.5 vs. 28.6 %, p = 0.279).

Conclusion

Although there was a little improvement in ovulation and pregnancy rates among patients with B and C phenotypes, there was not a statistically significant difference between the two groups. Based on our study, Metformin therapy does not change the ovulation and pregnancy rate.     

Alterations in thyroid function among the different polycystic ovary syndrome phenotypes

Abstract

The study evaluates the prevalence of subclinical thyroid dysfunction in infertile PCOS patients, according to the different PCOS phenotypes and to examine whether insulin sensitizers in insulin resistant (IR) PCOS patients may improve thyroid function. The study population consisted of all PCOS patients, attending the infertility and IVF unit of Department of Pediatrics, Obstetrics and Reproductive Medicine of University of Siena, Italy, and compared them to regularly cycling, healthy, infertile controls. Upon admission, blood was drawn from all patients during the early follicular phase, for complete hormonal and metabolic profiles. In IR-PCOS patients treated with insulin sensitizers, blood was drawn again after 6 months. PCOS patients had a significantly higher prevalence of subclinical thyroid dysfunction compared to infertile controls. While no significant association was detected between TSH value and the presence of hyperandrogenism, overweight and obese PCOS patients, as well as IR PCOS patients showed significantly higher prevalence of subclinical thyroid dysfunction. Moreover, among IR PCOS patients, 6 months treatment with insulin sensitizers significantly reduces TSH levels. Infertile PCOS patients have a high prevalence of subclinical thyroid dysfunction, which may be successfully treated in IR PCOS patients by insulin sensitizers.     

Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population

Aim. Our aim was to investigate the percentage occurrence of different phenotypes of polycystic ovary syndrome (PCOS) in a Bulgarian population, and their clinical, biochemical and hormonal characteristics.

Methods. The study included 70 women with PCOS, diagnosed according to the European Society of Human Reproduction & Embryology/American Society for Reproductive Medicine criteria. The women were divided into four phenotypes: hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovaries at ultrasound (PCO) (full-blown syndrome, phenotype A); HA + OA (former National Institutes of Health definition, phenotype B); OA + PCO (phenotype C); and HA + PCO (phenotype D). Serum levels of testosterone, immune-reactive insulin, sex hormone-binding globulin, dehydroepiandrosterone sulfate and lipid metabolism parameters were measured. Free androgen index and homeostasis model assessment of insulin resistance were calculated. Body mass index and waist-to-hip ratio were assessed.

Results. The percentages of phenotypes A, B, C and D in a Bulgarian population are 58.6%, 11.4%, 10.0% and 20.0%, respectively. The women with the classical form of PCOS (phenotypes A and B) were more obese, had more strongly expressed hyperandrogenemia, and were more insulin-resistant compared with the women of phenotypes C and D.

Conclusion. There is a significant difference in anthropometric, hormonal and metabolic indices between the classical form and the clinical variants of PCOS in the studied Bulgarian population.     

Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population.

AIM: Our aim was to investigate the percentage occurrence of different phenotypes of polycystic ovary syndrome (PCOS) in a Bulgarian population, and their clinical, biochemical and hormonal characteristics. METHODS: The study included 70 women with PCOS, diagnosed according to the European Society of Human Reproduction & Embryology/American Society for Reproductive Medicine criteria. The women were divided into four phenotypes: hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovaries at ultrasound (PCO) (full-blown syndrome, phenotype A); HA + OA (former National Institutes of Health definition, phenotype B); OA + PCO (phenotype C); and HA + PCO (phenotype D). Serum levels of testosterone, immune-reactive insulin, sex hormone-binding globulin, dehydroepiandrosterone sulfate and lipid metabolism parameters were measured. Free androgen index and homeostasis model assessment of insulin resistance were calculated. Body mass index and waist-to-hip ratio were assessed. RESULTS: The percentages of phenotypes A, B, C and D in a Bulgarian population are 58.6%, 11.4%, 10.0% and 20.0%, respectively. The women with the classical form of PCOS (phenotypes A and B) were more obese, had more strongly expressed hyperandrogenemia, and were more insulin-resistant compared with the women of phenotypes C and D. CONCLUSION: There is a significant difference in anthropometric, hormonal and metabolic indices between the classical form and the clinical variants of PCOS in the studied Bulgarian population.     

Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome patients with adrenal androgen excess

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA output in response to adrenocorticotropic hormone (ACTH), and that this abnormality is due to an identifiable alteration in the biosynthesis of AAs. DESIGN: Cross-sectional prospective controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Patients with PCOS (n = 9) and without (n = 9) AA excess and controls (n = 12) without hyperandrogenism, matched for age and body mass. INTERVENTION(S): Acute 60-minute ACTH test was performed on patients. MAIN OUTCOME MEASURE(S): Basal levels of dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, and basal (Steroid(0)) and the 60-minute ACTH-stimulated levels (Steroid(60)) of pregnenolone (PREG), progesterone (P4), 17-hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP), dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured. Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase were estimated from product to precursor ratio, using Steroid(60) values. RESULT(S): Compared with PCOS patients without AA excess, PCOS patients with AA excess demonstrated significantly greater levels of DHEA(0) and A4(60). PCOS patients with AA excess had significantly higher activity of delta(5)17-OH, compared with PCOS patients without AA excess. CONCLUSION(S): Adrenal androgen excess in PCOS is associated with a greater delta(5)17-OH activity in response to ACTH.     

Pioglitazone for treating polycystic ovary syndrome in non-obese women of reproductive age with different clinical presentations

Aims. To evaluate the effects of pioglitazone on menstruation and the metabolic parameters of non-obese women of reproductive age with polycystic ovary syndrome (PCOS) and compare the effects among different subgroups of PCOS patients with different clinical presentations.

Methods. Twenty-eight women of reproductive age with PCOS were recruited; 20 women finished the study. The women were divided into three groups according to clinical presentations: group A (n = 4) had chronic oligo- or anovulation with polycystic ovaries; group B (n = 5) had chronic oligo- or anovulation with hyperandrogenism; and group C (n = 11) had chronic oligo- or anovulation, hyperandrogenism and polycystic ovaries. Pioglitazone (15 mg/day) was given for 6 months and the therapeutic effects were evaluated. Menstrual cycle regularity and hormone levels (plasma luteinizing hormone (LH), follicle-stimulating hormone, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, glucose, insulin, C-peptide, free testosterone, homeostatic model assessment (HOMA)) were evaluated during and after pioglitazone treatment.

Results. Thirty percent and 45.5% of the patients showed improvement of menstrual cycle regularity immediately after completion of treatment and at 6 months after completion of pioglitazone treatment, respectively, although there were no statistical differences among the subgroups. There was a significant difference in the change of body mass index (BMI) throughout the study period among the subgroups (p = 0.008). The decrease in BMI was significantly higher in group B than in groups A and C at 3 months (p = 0.0381) and 6 months of treatment (p = 0.0054), as well as at 6 months after completion of treatment (p = 0.003). HDL-C concentrations increased throughout the period (p = 0.001) without a difference among the subgroups. LH levels decreased at 6 months of treatment and throughout the follow-up period (p = 0.0045), but this did not differ among subgroups. The free testosterone level decreased, but without significance. There was no statistical improvement in any of the parameters of insulin resistance, but baseline free testosterone levels were related to the improvement of the HOMA insulin sensitivity score (p = 0.0009). Patients with more than a 50% decrease of their HOMA insulin resistance (HOMA-IR) score showed higher baseline free testosterone levels (hyperandrogenic groups B and C) than did the patients with less than 50% HOMA-IR score improvement or those patients with an increased HOMA-IR score.

Conclusions. These preliminary results suggest that pioglitazone treatment for non-obese PCOS women of reproductive age may be effective to help the resumption of the menstrual cycle, and the patients showed a different response pattern according to their baseline free testosterone levels.     

Adrenal hyperresponsiveness to ACTH stimulation in women with polycystic ovary syndrome: an adrenarchal type of response

Adrenal responsiveness to ACTH stimulation (1 mg, i.m.) was assessed by measuring cortisol (Cort) and 17-hydroxyprogesterone (17OHP) at 0, 30, 60, and 90 minutes and progesterone (P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), delta 4-androstenedione (delta 4A), and testosterone (T) at 0, 60, and 90 minutes post-ACTH in 30 women with polycystic ovary syndrome (PCO). The results were compared with those from 12 normally menstruating women. Three distinct patterns of responses of the adrenal steroids were observed in PCO patients, while cortisol response was similar to that of normal controls: (a) normal responders (n = 9, 30% of PCO patients), in whom a delta max response similar to that of normals was observed, although basal delta 4A and T levels were found to be elevated; (b) 21-OH dysfunction group (n = 6, 16.6%), in whom delta max 17OHP levels and delta max 17OHP to delta max Cort ratio were significantly higher than those of normals and the other PCO groups, indicating a dysfunction at the 21-hydroxylase level; (c) adrenarchal type of response group (n = 16, 53%), in whom statistically significant (P less than .0001) hyperresponsiveness of DHEA and, in 11 of them, of delta 4A, with high delta max delta 4A to delta max DHEA to delta max Cort ratios were found, indicative of a selective overproduction of the steroids during steroidogenesis. Moreover, the significantly higher delta max delta 4A to delta max 17OHP ratio found in group c is a further indication of increased 17,20-lyase efficiency, as is encountered during adrenarche.(ABSTRACT TRUNCATED AT 250 WORDS)     

多囊卵巢综合征患者父母亲遗传表型的探讨

目的 探讨多囊卵巢综合征（ＰＣＯＳ）患者父母亲的遗传表型。方法 采用问卷表收集１３９例ＰＣＯＳ患者的父母亲和１３７名对照者父母亲的临床资料,比较母亲月经不规律、父亲早秃和父母亲高血压在两者间的发生频率,χ＾２检验差异显著的因素选入多因素Ｌｏｇｉｓｔｉｃ回归模型分析。结果 ＰＣＯＳ患者中,母亲月经不规律者占３８．１％、父亲早秃１９．４％、父亲高血压３０．９％,均明显高于对照者（分别为３．６％、５．１     

Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome

Aim.?This study was designed to examine the relationship between homocysteine (Hcy), lipoprotein levels and insulin resistance in obese and non-obese patients with polycystic ovary syndrome (PCOS).

Materials and methods.?Eighty-five patients (38 obese, 47 non-obese) with PCOS and 50 healthy subjects (25 obese, 25 non-obese) were included in the study. PCOS was defined according to the Homburg criterion. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), insulin, 17-hydroxyprogesterone, free testosterone, androstenedione, vitamin B₁₂ and folate were measured. Also, serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), apoprotein B (Apo B) and apoprotein A (Apo A) were determined. Plasma Hcy levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA).

Results.?Plasma Hcy levels were significantly higher in women with PCOS than in healthy women. HOMA-R (insulin resistance) was significantly higher in women with PCOS compared with healthy women. Serum fasting TC, LDL-C, TG, Apo B, vitamin B₁₂ and folate levels were similar between PCOS and control groups. Lp(a) levels were higher in PCOS patients than in control subjects, whereas HDL-C and Apo A levels were lower. Compared with obese PCOS subjects, non-obese PCOS subjects had low HOMA-R, TC, LDL-C, TG, Apo B, Lp(a) and androgen levels. Plasma Hcy levels, serum HDL-C and Apo A levels were similar between obese and non-obese women with PCOS. Levels of HDL-C and Apo A were lower in both obese and non-obese PCOS patients than in obese and non-obese control subjects, whereas Lp(a) levels were higher. No correlation was observed between plasma Hcy, body mass index, HOMA-R, serum androgen levels, TC, LDL-C, HDL-C, Apo A, Apo B and Lp(a) levels.

Conclusion.?These results showed that elevated insulin resistance and plasma Hcy levels, and changes in serum lipid profile, which are possible risk factors for cardiovascular disorders, play important roles in the development of cardiovascular disease in both obese and non-obese patients with PCOS.     

Adrenocortical response to ACTH stimulation in postmature newborns.

Diminished total plasma cortisol levels have been demonstrated in postmature neonates, suggesting that fetal glucocorticoids may be involved in the cause of postmaturity. This hypothesis was tested by adrenocortical stimulation in 32 newborns: 12 were postmature; 12 were postterm, but not postmature; and 8 were normal term neonates. The mean pre- and poststimulation total plasma cortisol levels were 3.9 and 50.9 microgram/100 ml, respectively, for the postmature newborns, 9.7 and 44.0 microgram/100 ml for the postterm, but nonpostmature newborns, and 9.8 and 37.1 microgram/100 ml for the normal term newborns. The differences in the poststimulation rise in plasma cortisol between the postmature and merely postterm infants or between the postterm and normal term infants were not statistically significant. The mean poststimulation cortisol rise in the postmature group exceeded that of the normal term group (P less than 0.05). The adequacy and promptness of response to adrenocortical stimulation eliminate the likelihood of adrenal insufficiency in postmature infants.     

Serum anti-mullerian hormone levels in the main phenotypes of polycystic ovary syndrome

Objective

To characterize the difference in circulating anti-Müllerian hormone (AMH) levels between the main polycystic ovary syndrome (PCOS) phenotypic groups and evaluate the role of AMH in predicting the severity of PCOS.

Study design

Cross-sectional, retrospective study. A total of 251 women were divided into four groups based on the main features of PCOS, as follows: Group 1 (polycystic ovarian morphology [PCOM]+/oligo-anovulation [OA]+/hyperandrogenism [HA]+), Group 2 (PCOM+/OA+/HA−), Group 3 (PCOM+/OA−/HA+), and Group 4 (PCOM−/OA+/HA+). AMH and other hormone levels were measured in serum. The main outcome was serum AMH concentrations in the main phenotypes of PCOS.

Result(s)

The mean serum AMH levels were 9.50 ± 6.1 ng/mL in Group 1; 8.02 ± 6.2 ng/mL in Group 2; 6.12 ± 3.6 ng/mL in Group 3; and 3.06 ± 2.4 ng/mL in Group 4. Circulating AMH levels in Group 1 (PCOM+/OA+/HA+) were three times higher than those in Group 4 (PCOM−/OA+/HA+).

Conclusions

The highest AMH levels were found in cases where all three main diagnostic criteria existed. AMH levels correlate best with PCOM. In addition, oligo-anovulation contributes to increased AMH levels. Hyperandrogenism criteria were found to have less influence on AMH levels. AMH levels seem to have a diagnostic role in determining the severity of PCOS.     

Clinical and laboratory indicators of polycystic ovary syndrome in Chinese Han nationality with different Rotterdam criteria-based phenotypes

The aim of this study was to investigate the clinical, endocrinic and metabolic indicators in polycystic ovary syndrome (PCOS) with different Rotterdam criteria (RC)-based subtypes, thus to guide the treatments. Six hundred and forty-seven PCOS cases were divided into four groups, with 60 cases set as the control group, the clinical and endocrinic indicators of different subtypes were evaluated. Group A was the most common and the most serious (63.2%), while group B was the least (9%). The clinical signs, as well as the endocrinic and metabolic characteristics, of the two groups were similar, but group A exhibited higher androgen level and hirsutism score. The phenotypes of group C (15.6%) and group D (12.9%) were mild, but compared with the control group, luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) were significantly increased. Insulin resistance in these four subtypes were positively correlated with apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1), while only positively correlated with serum total testosterone, and negatively correlated with LH/FSH in group A. RC-PCOS typing could reflect the basic characteristics of the disease. Hyperandrogenism was the main basis for distinguishing PCOS, although the non-hyperandrogenism group could represent a relatively mild phenotype of PCOS, there might exist different pathogenic pathways.