Gürkan Uncu

Prospective assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve

STUDY QUESTION Do the presence of endometriomas and their laparoscopic excision lead to a decrease in ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER Both the presence and excision of endometriomas cause a significant decrease in serum AMH levels, which is sustained 6 months after surgery. WHAT IS KNOWN ALREADY No previous comparison of serum AMH levels between women with and without endometrioma has been reported. However, studies have suggested a decline in serum AMH levels 1-3 months after endometrioma excision but long-term data are needed. STUDY DESIGN, SIZE, DURATION A prospective cohort study including 30 women with endometrioma >2 cm were age matched with 30 healthy women without ovarian cysts. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with endometrioma underwent laparoscopic excision with the stripping technique. Serum AMH level and antral follicle count (AFC) were determined preoperatively, 1 and 6 months after surgery. Correlation analyses were undertaken in order to identify determinants of surgery-related change in ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE Compared with controls at baseline, women with endometrioma had lower AMH levels (4.2 ± 2.3 versus 2.8 ± 2.2 ng/ml, respectively, P = 0.02) and AFC (14.7 ± 4.1 versus 9.7 ± 4.8, respectively, P < 0.01). Serum AMH levels were further decreased 6 months after surgery (2.8 ± 2.2 versus 1.8 ± 1.3 ng/ml, P = 0.02), while AFC remained unchanged (9.7 ± 4.8 versus 10.4 ± 4.2, P = 0.63). The rate of decline in AMH was not correlated with age, laterality of endometrioma, cyst diameter or the number of primordial follicles on the surgical specimens. The preoperative serum AMH level was positively correlated with the rate of decline in serum AMH after surgery (r = 0.47, P = 0.02). LIMITATIONS, REASONS FOR CAUTION The absence of a non-treated group of women with endometriomas as a further control prevents comment on the presence of a progressive decline in ovarian reserve related to endometrioma per se. The sample size may be too small for detection of factors correlated with the extent of ovarian damage. WIDER IMPLICATIONS OF THE FINDINGS While the findings are mostly in agreement with previous studies, the present study is the first to show that the presence of endometrioma per se is associated with a decrease in ovarian reserve. The extent of surgery-related decline in ovarian reserve is not predictable using preoperative or perioperative factors. It may be prudent to measure AMH levels preoperatively and delay/avoid surgical excision as far as is possible if subsequent fertility is a concern. Additional studies are required to further investigate whether the endometrioma-related decline in ovarian reserve per se is progressive in nature and whether it exceeds the surgery-related decline. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Research Fund of the Uludag University School of Medicine. The authors have no conflict of interest associated with this study.

Free and Phospholipid-Bound Choline Concentrations in Serum during Pregnancy, after Delivery and in Newborns

The aims of this study were to determine whether serum free choline and phospholipid-bound choline concentrations change during the pregnancy or after childbirth and to determine if the serum choline concentrations of the mother and newborn are correlated. Serum free and bound choline concentrations were 10.7 ± 0.5 µM and 2780 ± 95 µM in control, non-pregnant women, and rose significantly (p < 0.001) to 14.5 ± 0.6 µM and 3370 ± 50 µM or to 16.5 ± 0.7 µM and 3520 ± 150 µM after 16-20 weeks or 36-40 weeks of pregnancy, respectively. Serum free and phospholipid-bound choline fell by 14-22% (p < 0.05-01) after either vaginal delivery or caesarian section, and remained low (by 15-42%; p < 0.05-0.001) for 12h and then rose toward the baseline within 24h. In amniotic fluid, free choline and phospholipidbound choline concentrations were 22.8 ± 1.0 and 19.6 ± 0.8 µM or 24.0 ± 1.5 and 516 ± 43 µM at 16-20 weeks of gestational age or at term, respectively. In newborns, serum free choline concentrations were higher (p < 0.001) and phospholipid-bound choline concentrations were lower (p < 0.001) than in their mothers. These results show that serum free choline and phospholipid-bound choline concentrations are elevated during the pregnancy, which may be required for an adequate maternal supply of choline to the fetus. These observations are clinically important to determine the ideal dietary intake of choline during the pregnancy.

The effects of different hormone replacement therapy regimens on tear function, intraocular pressure and lens opacity

Objective. Estrogen may have adverse effects on the ocular surface, intraocular pressure (IOP), lens opacity and tear function. The aim of the present study was to elucidate the effects of different hormone replacement therapy (HRT) protocols on tear function, IOP and lens opacity. Design and setting. This was a prospective, uncontrolled study carried out at the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Uludağ University, Turkey. Patients and interventions. Thirty postmenopausal patients who had spontaneous or surgical menopause for at least 1 year and were not taking any medications were assigned to one of three groups. Group 1 comprised 19 patients (n = 38 observations) given conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg (Premelle 2.5®) daily; Group 2 contained six patients (n = 12 observations) given tibolone 2.5 mg (Livial®) daily; and Group 3 comprised five patients (n = 10 observations) treated with estradiol patch, 3.9 mg/12 cm2 (Climara®). Tear function, evaluated with Schirmers test, IOP and lens opacity were determined before treatment and at 6 and 12 months of treatment. Results. Mean Schirmers test score in each group and all eyes (n = 60) did not change significantly after 6 months of treatment but decreased significantly at 12 months. The percentage decrease in tear function was greatest in the estrogen-only group (Group 3). Mean IOP did not change significantly in Groups 1 and 2; however, in Group 3, IOP showed a statistically significant decrease from 14.63 ± 0.84 mmHg before treatment to 12.60 ± 0.68 mmHg (mean ± standard error) at the end of treatment. Lens opacity in women of all groups did not change during treatment. Conclusions. HRT decreased tear production, the decrease being greater in the estrogen- only group. Woman who are taking or considering HRT should be informed of the potential increased risk of dry eye syndrome with this therapy. In addition, estrogen-only treatment decreased IOP while estrogen plus progesterone and tibolone had no effect. HRT did not affect lens opacity after 12 months of treatment.

Evaluation of serum creatine kinase in ectopic pregnancy with reference to tubal status and histopathology

Objective To study the value of creatine kinase in ectopic pregnancy with reference to tubal histopathology.

The decline in serum choline concentration in humans during and after surgery is associated with the elevation of cortisol, adrenocorticotropic hormone, prolactin and β-endorphin concentrations

Serum choline concentrations decrease during and after surgery. We undertook this study to determine whether the decrease of choline is associated with an increase in stress hormones. In 16 patients undergoing abdominal surgery with general anesthesia, circulating choline cortisol, prolactin, adrenocorticotropic hormone (ACTH) and -endorphin levels were measured before, during and after surgery. Choline levels decreased by 41% (P<0.01) during surgery, remained 15-38% decreased for 48 h, and returned to preoperative values 72 h after surgery. The decrease in serum choline was associated and inversely correlated with the increase in serum cortisol (P<0.001; r = -0.642), prolactin (P<0.001; r = -0.756), -endorphin (P<0.001; r = -0.726) and ACTH (P<0.01; r = -0.458). In conclusion, we found that abdominal surgery induces a decline in serum choline associated with an increase in circulating cortisol, prolactin, ACTH and -endorphin.

Plasma interleukin-1α, interleukin-1β and interleukin-1 receptor antagonist levels in pre-eclampsia

Abstract The values of plasma interleukin-1α (IL-1α), interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) levels were evaluated as the markers of pre-eclampsia in 35 serial plasma samples from ten pregnant women who subsequently developed pre-eclampsia and in 74 plasma samples from 20 uncomplicated pregnancies, retrospectively. No correlation was found between plasma IL-1α, IL-1β and IL-1ra levels, liver and renal function tests. thrombocyte and white blood cell counts, proteinuria, systolic and diastolic blood pressures and gestational weeks. Almost equal levels of IL-1α and IL-1β were measured in all corresponding groups, but these were too few in number to statistically analyze. IL-1ra values were higher in the pre-eclampsia group than in the uncomplicated pregnancy group, at 20–25 and 31–35 gestational weeks significantly and 26–30 gestational weeks insignificantly and showed an increase during labor in both groups. It was found to have 58% positive predictivity, 100% negative predictivity, 50% specificity and 100% sensitivity at gestational weeks 20–25. According to these results, IL-1ra seems to be considered for its high negative predictivity in the exclusion of the probability of pre-eclampsia development during antenatal visits, but its plasma level is not correlated with the severity of the disease.

Declines in serum free and bound choline concentrations in humans after three different types of major surgery

Abstract We examined the changes in circulating choline status in humans in response to major surgery by measuring serum free and phospholipid-bound choline concentrations before, during and 1–72h after total abdominal hysterectomy, off-pump coronary artery graft surgery or brain tumor surgery. Preoperatively, the mean serum free and phospholipid-bound choline concentrations in patients scheduled for abdominal hysterectomy (n=26), off-pump coronary artery grafting surgery (n=34) or brain tumor surgery (n=24) were 12.3±0.5, 12.1±0.4 and 11.4±0.4μmol/l, and 2495±75, 2590±115 and 2625±80μmol/l, respectively. Serum free choline and phospholipid-bound choline concentrations decreased from these baseline values to 8.8±0.7 (p<0.001), 8.8±0.5 (p<0.001) and 8.2±0.4μmol/l (p<0.001), and 2050±108 (p<0.001), 2166±59 (p<0.001) and 1884±104μmol/l (p<0.001) at 1h after hysterectomy, off-pump bypass graft surgery or brain tumor surgery, respectively. They remained at these low levels for 24h and then gradually increased towards the preoperative values at 48–72h postoperatively. Serum cortisol increased postoperatively in all surgical patients for 24h and its levels were inversely correlated with serum free and bound choline concentrations. These results show that circulating free and bound choline concentrations decrease for 72h after total abdominal hysterectomy, off-pump coronary artery graft surgery or brain tumor surgery in humans.

The Impact of Endometriosis and Its Treatment on Ovarian Reserve.

Endometriosis is a chronic disease mostly affecting women at reproductive age. There is a clear association between endometriosis and infertility; however, exact mechanisms are unknown. Some evidence suggests an adverse effect on oocytes. Endometriosis and its surgical treatment can affect quantitative ovarian reserve as well. In the presence of endometriomas, serum level of anti-Müllerian hormone (AMH) seems a more reliable marker of ovarian reserve than antral follicle count. Women with endometrioma have decreased serum AMH levels as compared with healthy controls. This is further declined after surgical excision, and the decline seems permanent. Bipolar cauterization of the ovary seems to be playing a role on ovarian damage. Extraovarian endometriosis and its surgical treatment can also be associated with decreased ovarian reserve, but there is limited information. Patients with endometriosis should be informed about fertility preservation options, especially in the presence of bilateral endometriomas or prior to surgery.

Impact of endometriomas and their removal on ovarian reserve.

Purpose of review The effect of endometrioma on ovulatory function and ovarian reserve was unclear. Conflicting opinions exist regarding effect of endometrioma excision on ovarian reserve. Recent findings Endometriomas do not seem to affect ovulatory function. Women with endometrioma have lower antral follicle count and serum anti-Müllerian hormone levels than age-matched healthy controls. There is high-quality evidence suggesting a significant decline in serum anti-Müllerian hormone levels following endometrioma excision. However, a similarly significant decline in antral follicle count is not demonstrated. Cauterization seems to be a contributing factor to ovarian damage and suturing the cyst bed could perhaps be a better alternative. Summary It seems prudent to warn patients regarding loss of ovarian reserve following endometrioma excision. Surgeons should cautiously limit the use of cauterization following stripping of endometrioma. Well designed studies comparing effect of various haemostatic measures on ovarian reserve are needed.

The role of plasma renin activity in distinguishing patients with polycystic ovary syndrome (PCOS) from oligomenorrheic patients without PCOS

All the components of the renin-angiotensin system have been identified in the human ovary. Renin plays a major role in folliculogenesis, and possibly in follicular atresia. Polycystic ovary syndrome (PCOS) is characterized by early follicular atresia. We studied whether assessment of plasma renin activity would be useful for diagnosing PCOS and distinguishing PCOS and non-PCOS in oligomenorrheic patients. Patients were divided into three groups: PCOS group (group 1, n = 40), non-PCOS oligomenorrheic group (group 2, n = 30) and ovulatory control group (group 3, n = 30). Plasma renin activity was determined in the early follicular phase of the menstrual cycle. Baseline serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, aldosterone and androgens (total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and 17α hydroxyprogesterone) were determined in all groups. The mean LH level was lower (4.94 ± 4.65 mIU/ml) in control patients than in PCOS patients (12.9 ± 1.75 mIU/ml) and non-PCOS oligomenorrheic patients (10.8 ± 1.65 mIU/ml). There was no statistically significant difference between the groups regarding FSH levels. The mean plasma renin activity was 3.47 ± 0.29 ng/ml in the PCOS group. The mean plasma renin activity was 1.59 ± 0.21 ng/ml the non-PCOS oligomenorrheic group (statistically significiant differrence). There was no statistically significant difference between the non-PCOS oligomenorrheic (1.59 ± 0.21 ng/ml) and control groups (1.2 ± 0.16 ng/ml). Use of plasma renin activity alone as a diagnostic marker in PCOS is not useful, because the clinical findings of PCOS are heterogeneous and the pathogenesis is unclear. However, it can be used together with other variables to diagnose women with PCOS and to distinguish non-PCOS oligomenorrheic women from those with PCOS.