Artemis Karkanaki

Phenotypic expression, body mass index and insulin resistance in relation to LH levels in women with polycystic ovary syndrome

OBJECTIVE To evaluate LH levels in women with the classic (1990 criteria) and the newer (2003 criteria) PCOS phenotypes, and to examine the impact of BMI and insulin resistance indices on hormone levels. STUDY DESIGN In this controlled clinical study 936 women with PCOS, classified as classic (n=729) and newer (n=207), and 204 controls were included. All women were divided into normal-weight (BMI<25 kg/m(2)) and overweight plus obese (BMI≥25 kg/m(2)). Serum LH, FSH, anthropometrics, androgens, fasting insulin and glucose, HoMA-IR, number of follicles, and ovarian volume were assessed. RESULTS Women with classic PCOS presented significantly higher LH and LH/FSH ratios, and lower glucose/insulin levels than those with the newer phenotype and controls. Overweight plus obese women of all groups had lower LH levels than normal-weight women. Independent positive correlations between LH and androgens and negative correlation between LH and BMI were found. CONCLUSIONS The higher LH concentrations of the classic phenotypes of PCOS could be attributed to the higher androgen levels, which desensitize the hypothalamus to the negative feedback regulation by progesterone. Moreover, the lower LH levels of overweight plus obese women of all groups could be attributed to the increased peripheral aromatization of androgens to estrogens in adipose tissue leading to suppression of LH secretion. CONDENSATION Both normal-weight and overweight women with classic PCOS phenotypes present higher LH levels and LH-to-FSH ratios than women with similar BMI but the newer phenotypes.

Serum Anti-Müllerian hormone (AMH) levels are differentially modulated by both serum gonadotropins and not only by serum Follicle Stimulating Hormone (FSH) levels

It is generally accepted that serum AMH levels are thought to reflect the size of the ovarian follicle pool. Therefore, an inverse correlation between serum AMH and Follicle Stimulating Hormone (FSH) levels has been noted in older women with abnormal or exhausted follicular development, such as menopause, leading to the use of serum AMH as a marker of ovarian reserve. In clinical practice the use of serum AMH for the assessment of ovarian reserve has been expanding to women irrespective of age, such as women in early menopause or women undergoing ovarian stimulation for in vitro fertilization (IVF). To our knowledge, this opinion article aims to show that serum AMH levels are differentially modulated by both serum gonadotropins, depending on the degree of ovarian reserve. For instance, in conditions of increased LH and normal to low FSH such as young PCOS women with hyperandrogenemia, serum AMH levels are increased and tend to be associated to serum LH, while in conditions of increased FSH such as premature ovarian failure, serum AMH levels are decreased and tend to be associated to serum FSH. The evidence that supports the theory of a link between AMH and LH in PCOS comes from both in vitro and in vivo experiments. Serum AMH levels have been directly linked to serum LH levels in the most severe forms of PCOS. LH has also been shown in vitro to directly increase serum AMH levels in PCOS derived granulosa cells. Finally, hyperandrogenism, obesity, insulin resistance and OCs administration, indirectly affect serum AMH levels, by modulating serum LH. Concerning PCOS, the correlation between AMH and LH can be used in the future for the assessment of the severity of PCOS, of the amelioration of PCOS under OCs treatment, as well as of the efficacy of infertility treatment in clomiphene resistant PCOS women. Apart from PCOS, the clinical implications of this theoretical approach might become important in a variety of medical conditions. For instance, serum AMH levels might be used in the future as a marker of cysts formation in the ovaries as well as of ovarian endometriosis, or as a marker of ovarian response to treatment of ovarian cysts or ovarian endometriosis by oral contraceptives, etc. Additionally, in infertile women with hypothalamic amenorrhea, serum AMH levels might be used for the assessment of ovarian recovery under treatment.

Decreased active, total and altered active to total ghrelin ratio in normal weight women with the more severe form of polycystic ovary syndrome

OBJECTIVE To assess total, active and active to total serum ghrelin ratio in normal weight women with polycystic ovary syndrome (PCOS) and in healthy ovulatory control women. STUDY DESIGN The study included 50 normal weight women with PCOS with a mean age of 23.70+/-4.99 years and 10 control women with a mean age of 30+/-5.80 years. The diagnosis of PCOS was based on the presence of biochemical hyperandrogenemia, chronic anovulation and polycystic ovarian morphology according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Serum total and active ghrelin were measured by RIA, using commercially available kits. RESULTS A significantly lower serum active/total ghrelin ratio was noted in the more severe form of PCOS with hyperandrogenemia, chronic anovulation and polycystic ovarian morphology. Both total and active serum ghrelin levels were negatively correlated to hirsutism score, to plasma glucose levels and to QUICKI and HOMA-IR indices of Insulin Resistance. A statistically significant difference was detected between the more severe and the milder forms of PCOS, concerning serum levels of total ghrelin (p=0.017), active ghrelin (p=0.007) and the active/total ghrelin ratio (p=0.026). CONCLUSIONS The results of the present study demonstrate an altered active to total ghrelin ratio, as well as a tendency towards lower both total and active fasting serum ghrelin levels in normal weight PCOS, more pronounced in the more severe forms of the syndrome.

Adiponectin levels reflect the different phenotypes of polycystic ovary syndrome: study in normal weight, normoinsulinemic patients

Diagnosis of polycystic ovary syndrome (PCOS), at present very common in women of reproductive age, is implicated with potential long-term metabolic consequences that are difficult to be investigated due to the heterogeneity in the manifestation of the syndrome. The present study constitutes an effort to explore the graduated metabolic impact of the different PCOS phenotypic groups through the levels of adiponectin, an adipose-derived hormone, in 100 normal weight, normoinsulinemic patients with PCOS.

Operator experience reduces the risk of second trimester amniocentesis-related adverse outcomes

OBJECTIVE To investigate the impact of operator experience on amniocentesis-related adverse outcomes. STUDY DESIGN Retrospective study of mid-trimester amniocenteses performed by the same operator on singleton pregnancies in a single private institution during 1994-2007. Outcomes were hemorrhagic or dark amniotic fluid aspiration, insufficient volume aspiration, repeated puncture and fetal loss. Rates were estimated annually, as well as for every 10% of procedures up to the total number. The association of each outcome with epidemiological aspects was also examined. RESULTS In total, 5913 amniocenteses were performed. The overall rate of adverse outcomes was 5.4%. The total adverse outcome rate reduced from 10.2% in the first 10% of cases to 3.0% in the last 10% (P=.001). The rate of hemorrhagic fluid gradually decreased from 4.4% to 1.5% (P=.05) over the same intervals. The fetal loss rate was also reduced from 0.5% during the first half to 0.3% in the second half of the study period (P=NS). Logistic regression analysis indicated no significant correlations between adverse outcomes with any of epidemiological parameters of women undergoing amniocentesis. CONCLUSION Operator experience has a beneficial impact on preventing procedure-related adverse outcomes.

Amniocentesis-related adverse outcomes in diamniotic twins: is there a difference compared to singleton pregnancies?

OBJECTIVE To investigate whether diamniotic twin gestations are at increased risk of amniocentesis-related adverse outcomes compared to singleton pregnancies. STUDY DESIGN This was a retrospective study of mid-trimester amniocenteses performed during the period 1993-2009. Cases were divided in two groups, one including singleton (Group 1) and the other diamniotic twin pregnancies (Group 2). All amniocentesis-related adverse outcomes were reviewed, including aspiration of insufficient amniotic fluid, aspiration of hemorrhagic amniotic fluid, repeated puncture and miscarriage. The incidence of these adverse outcomes was compared between the two groups. RESULTS In total, 6270 cases were included in the study (Group 1, n=6150 and Group 2, n=120). Advanced maternal age was the main indication for amniocentesis in both singleton and twin pregnancies. There was no difference in the incidence of insufficient sample aspiration (0.2% in singletons vs. 0.0% in twins, P=NS), in the incidence of blood-stained amniotic fluid (3.7% in singletons vs. 4.6% in twins, P=NS), in the rate of need for second attempt (2.1% in singletons vs. 1.7% in twins, P=NS) or in the miscarriage rate (0.24% in singletons vs. 0% in twins). CONCLUSION In our experience, the incidence of amniocentesis-related adverse outcomes is not increased in diamniotic twins compared to singleton pregnancies.

Is the Risk for Cardiovascular Disease Increased in all Phenotypes of the Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age, affecting around 10% of them. Polycystic ovary syndrome is considered to be related to increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There are 2 definitions for PCOS: one adopted in 1990 (classical PCOS with phenotypes A and B) and the otherin 2003 (Rotterdam criteria with 4 phenotypes A to D). The latter is a wider definition including the 1990 phenotypes. There is mounting data suggesting that phenotypes C and D are not actually related to increased CVD risk, and thus screening for CVD risk factors of intervening for primary CVD prevention in young women is not cost-effective. There is an increasing number of suggestions to return to the 1990 criteria plus some metabolic parameters to identify real CVD risk in this population. However, such a strategy needs verification by large, prospective studies.

Ultrasound and PCOS

Polycystic ovary syndrome (PCOS) is a common medical entity affecting up to 10 % of women of reproductive age. Until 2003, when polycystic ovarian morphology was included, the diagnosis of PCOS was based on the presence of clinical or laboratory evidence of hyperandrogenemia and chronic oligo- or anovulation. Despite the name of the syndrome, the polycystic ovarian morphology was not considered pathognomonic for the diagnosis. During the Consensus Workshop in Rotterdam, the sonographic evidence of polycystic morphology was recognized as equal diagnostic criterion of the syndrome and was further defined and simplified into the presence of either 12 or more follicles of 2–9 mm of diameter or an increased ovarian volume of more than 10 cm3. Thereafter, the technical refinement of the ultrasound equipment, the introduction of three-dimensional imaging, the rise of four distinct phenotypes of the syndrome, the connection of PCOS with metabolic disturbances and infertility implications, the results of well-designed studies, and, finally, the inherent trend for improvement of the clinical practice brought to the surface the necessity to fine-tune the definition of polycystic ovarian morphology. In this direction, there have been proposals to modify the threshold in the number of the antral follicles and the ovarian volume, according to the results of subsequent studies. Other researchers supported the role of three-dimensional screening as it provides better spatial perception and, consequently, more accurate follicle count. Additionally, 3D ultrasound offers the possibility to assess the degree of stromal echogenicity and vascularization that could be important features of the syndrome in combination with the peripheral distribution of the follicles. The substitution of ultrasound examination by anti-Mullerian hormone (AMH) measurement has also been proposed as a more precise method of evaluation of the ovarian function and reserve, especially in cases of controlled ovarian stimulation. All these controversies have been proven creative and will lead to a promising future of the ultrasound imaging in the diagnosis, definition, and treatment of the clinical manifestations of PCOS as acne, anovulation, and most importantly infertility.

Effects of Lifestyle Modification on Pregnancy Success in Obese and Overweight Women with PCOS

The present review approaches the pregnancy success after lifestyle modification in obese infertile women with Polycystic Ovary Syndrome (PCOS). Lifestyle modification including hypocaloric diet, structured exercise and counseling, in combination with medical intervention, where necessary, is effective on the resumption of menstruation, the amelioration of the reproductive profile and the success of spontaneous pregnancy. Pregnancy rates vary a lot among the studies. There are limitations due to the heterogeneity in the design of the studies, the diagnosis of the syndrome and the type of the intervention. The number of the studies is restricted and raises the need for further evaluation through well designed, controlled trials. Despite the controversies, the evidence supports the lifestyle modification as first line therapy in obese and overweight women with PCOS.