Saad Amer

The Impact of Excision of Ovarian Endometrioma on Ovarian Reserve: A Systematic Review and Meta-Analysis

CONTEXT Endometriomas are mainly treated surgically. However, there has been concern over the potential damaging effect of this surgery on ovarian reserve. OBJECTIVE The aim of this meta-analysis was to investigate the impact of surgery for endometriomas on ovarian reserve as determined by serum anti-müllerian hormone (AMH). DATA SOURCES MEDLINE, PubMed, and Embase were searched electronically. STUDY SELECTION All prospective cohort studies that analyzed changes of serum AMH concentrations after surgical treatment of endometriomas were eligible. Twenty-one studies were identified, of which eight were selected for meta-analysis. DATA EXTRACTION Two reviewers performed the data extraction independently. DATA SYNTHESIS Pooled analysis of 237 patients showed a statistically significant decrease in serum AMH concentration after ovarian cystectomy (weighted mean difference -1.13 ng/ml; 95% confidence interval -0.37 to -1.88), although heterogeneity was high. Sensitivity analysis for studies with a preoperative serum AMH level of 3.1 ng/ml or greater improved heterogeneity but also still showed a significant postoperative fall in serum AMH (weighted mean difference -1.52 ng/ml, 95% confidence interval -1.04 to -2). CONCLUSION The results of this study suggest a negative impact of excision of endometriomas on ovarian reserve as evidenced by a significant postoperative fall in circulating AMH.

The value of measuring anti-Müllerian hormone in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy

BACKGROUND Anti-Müllerian hormone (AMH) has been implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to measure circulating AMH before laparoscopic ovarian diathermy (LOD) to evaluate its prognostic value for an ovulatory response and to investigate AMH changes after LOD to further explore the effects of LOD. METHODS This prospective study included anovulatory women with PCOS undergoing LOD (n = 29) or receiving clomiphene citrate (n = 18). Plasma AMH concentrations were measured before and 1 week after treatment. Further measurements of AMH were made at 3- and 6-month follow-up. RESULTS The pretreatment median (range) plasma AMH concentrations were 6.1 (1.0-21.0) and 5.7 (1.3-9.5) ng/ml in women having LOD and clomiphene citrate treatment, respectively. Women who ovulated after LOD (n = 24) had a significantly (P = 0.032) lower pre-operative AMH [5.6 (1.0-21.0) ng/ml] compared with the non-responders [9.0 (6.1-17.1) ng/ml]. Using receiver-operating characteristic curve analysis, AMH was found to be a useful predictor of no ovulation after LOD with area under the curve of 0.804 (P = 0.025). Using a cut-off of 7.7 ng/ml, AMH had a sensitivity of 78% and a specificity of 76% in the prediction of no ovulation after LOD. For all patients (n = 47, clomiphene citrate or LOD), plasma AMH >or=7.7 ng/ml was associated with a reduced chance of ovulation after treatment (P = 0.004). Following LOD, the median AMH concentration significantly (P = 0.003) decreased to 4.7 (0.3-15.1) ng/ml and remained low at 3- and 6-month follow-up. CONCLUSIONS Pretreatment circulating AMH level seems to be a good predictor of the ovarian response to LOD.

Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome

BACKGROUND Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment. METHODS The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI). RESULTS After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)]. CONCLUSIONS LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545.

An analysis of the pattern of pregnancy loss in women with recurrent miscarriage

OBJECTIVE To describe the pattern of pregnancy loss in women with a history of recurrent miscarriage (RM). DESIGN Retrospective, observational study. SETTING A tertiary referral center for RM. PATIENT(S) Five hundred thirty-eight subjects with RM. INTERVENTION(S) Women with antiphospholipid syndrome were treated with clexane and aspirin; some patients with uterine anomalies underwent corrective surgery, and some cases of retarded endometrium were treated with hMG. MAIN OUTCOME MEASURE(S) Pregnancy outcome, including the stage of pregnancy at which pregnancy loss occurred. RESULT(S) In women with a prothrombotic state, the miscarriage rate before the detection of fetal heart activity (early loss) in the untreated group (50%) was significantly higher than in the treatment group (17.5%). In women with a uterine anomaly, the early loss rate and the later loss rate (after detection of fetal heart activity) were both increased. Women with retarded endometrium, women with >/=6 losses, and older women (>/=41 years) are more likely to have a further early loss but not a later loss. CONCLUSION(S) An understanding of the patterns of pregnancy loss provides further insight into the mechanism of the reproductive failure, which has implications for treatment.

The expression of inducible nitric oxide synthase in the human fallopian tube during the menstrual cycle and in ectopic pregnancy

OBJECTIVE To investigate the production of inducible nitric oxide synthase (iNOS) in the fallopian tube (FT) during the menstrual cycle and whether epithelia from FTs bearing an ectopic pregnancy differ from healthy tubes in iNOS expression. DESIGN Prospective study. SETTING Academic unit of reproductive and developmental medicine. PATIENT(S) Fallopian tubes from the different stages of the menstrual cycle (n=12), FTs bearing an ectopic pregnancy (n=15), and FTs from pseudopregnant women (n=6) were collected. INTERVENTION(S) In the pseudopregnant group, patients were injected with hCG in the days leading up to hysterectomy. Samples were processed for immunohistochemistry staining and quantitative reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURE(S) To compare iNOS protein and messenger RNA expression between the different groups. RESULT(S) This is the first report on cyclicity in iNOS production by human fallopian tube during the menstrual cycle. The intensity of expression of iNOS was higher in the ectopic pregnancy group compared with the pseudopregnant group (P<0.05). CONCLUSION(S) The cyclicity in iNOS expression by the tube suggests its involvement in fertilization and early embryonic development. Pathologic generation of nitric oxide through increase iNOS production may decrease tubal ciliary beats and smooth muscle contractions and thus affect embryo transport, which may consequently result in ectopic pregnancy.

The Predictive Value of Circulating Anti-Müllerian Hormone in Women With Polycystic Ovarian Syndrome Receiving Clomiphene Citrate: A Prospective Observational Study

CONTEXT Elevated serum anti-Müllerian hormone (AMH) concentration in women with polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian follicles to circulating FSH. This effect may compromise the outcome of clomiphene citrate (CC) ovulation induction. OBJECTIVE The objective of the study was to investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. DESIGN This was a prospective cohort observational study. SETTING The study was conducted at the Fertility Unit, Derby, United Kingdom. PATIENTS Sixty anovulatory women with PCOS participated in the study. INTERVENTIONS Serum AMH concentrations were measured on cycle day 2 during 187 CC cycles. These concentrations were compared between responders and nonresponders. The receiver-operating characteristic curve was used to evaluate the prognostic value of circulating AMH. The success rates of CC were compared between patients with high vs low AMH levels. The dose of CC required to achieve ovulation was correlated with serum AMH concentrations. MAIN OUTCOME MEASURES Ovulation and pregnancy rates were measured. RESULTS Serum AMH concentrations were significantly (P < .001) lower in responders (achieving ovulation) vs nonresponders (mean ± SEM, 2.5 ± 0.1 vs 5.8 ± 0.7 ng/mL, respectively). Similarly, serum AMH concentrations were significantly (P = .046) lower in pregnant (3.0 ± 0.4 ng/mL) vs nonpregnant patients (4.4 ± 0.5 ng/mL). There was a significant (P = .02) gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation. The receiver-operating characteristic curve showed AMH to be a useful predictor of no ovulation (area under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL. Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%, P = .034) in patients with low AMH (<3.4 ng/mL) vs women with AMH 3.4 ng/mL or greater (48% and 19%). CONCLUSION PCOS women with high circulating AMH (≥ 3.4 ng/mL) seem to be resistant to CC and may require a higher starting dose.

Repeated laparoscopic ovarian diathermy is effective in women with anovulatory infertility due to polycystic ovary syndrome

OBJECTIVE To assess the effectiveness of a second laparoscopic ovarian diathermy (LOD) in women with polycystic ovary syndrome (PCOS). DESIGN Retrospective study. SETTING Tertiary infertility clinic. PATIENT(S) Twenty anovulatory infertile women with PCOS who underwent LOD 1-6 years previously. Twelve subjects had previously responded positively to the first LOD, but the anovulatory status recurred (Group I), whereas eight subjects had not responded at all (Group II). INTERVENTION(S) Laparoscopic ovarian diathermy. MAIN OUTCOME MEASURE(S) Rates of ovulation, pregnancy and resumption of menstrual regularity, and biochemical changes. RESULT(S) An overall ovulation rate of 12 out of 20 women (60%) and a pregnancy rate of 10 out of 19 (53%) were achieved after the second LOD. In women (n = 12) who previously responded positively to the first LOD (LOD-sensitive), the ovulation and pregnancy rates were 10 out of 12 (83%) and 8 out of 12 women (67%), respectively, which were significantly (P<.05) higher than 2 out of 8 (25%) and 2 out of 7 (29%) of the previous nonresponders (LOD-resistant). Statistically significant hormonal changes including reduction of luteinizing hormone (LH), testosterone (T), and free androgen index (FAI) after the repeat LOD were only observed in the LOD-sensitive group. CONCLUSION(S) Repeat LOD is highly effective in women who previously responded to the first procedure.

An RCT of metformin versus orlistat for the management of obese anovulatory women

BACKGROUND Treatment of obesity-related anovulation poses a significant clinical challenge. Occasionally, the use of antiobesity medications such as orlistat or insulin sensitizing agents such as metformin is sometimes indicated in these patients. This study aimed to compare the effects of metformin and orlistat for improving ovulation in obese anovulatory women. METHODS This was an open-label RCT. A total of 40 women were randomized to receive either metformin (n = 20) or orlistat (n = 20). BMI as well as the androgen profile and the ovulatory status were assessed at baseline and at four weekly intervals for 3 months. Different anthropometric and endocrine parameters were also assessed as possible predictors of ovulation. RESULTS There was no significant difference between the two study arms regarding the ovulation rate for metformin and orlistat [40% (n = 8/20) and 25% (n = 5/20), respectively, P = 0.31]. Both arms showed a significant drop in the BMI, testosterone and androstendione concentrations (P < 0.05), but there was no difference between the two arms. Patients who ovulated had significantly lower concentrations of baseline LH, androstendione, dehydroepiandrosterone and free androgen index (P < 0.05). Among these factors, a low baseline LH was found to be the only independent predictor of ovulation (area under curve, 0.85). CONCLUSIONS Both metformin and orlistat show a similar effect on weight loss, ovulation rates and androgen concentrations. However, the effects on ovulation rates need to be confirmed in larger studies. The presence of a low baseline serum LH was found to be the most important predictor of ovulation. The study was registered at clinicaltrials.gov. NCT00292799.

The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study.

BackgroundWomen with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women.MethodsThis prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations.ResultsCycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (<4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20 {12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14}days).ConclusionsPCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.

The validity of transvaginal ultrasound measurement of endometrial thickness: a comparison of ultrasound measurement with direct anatomical measurement.

Objectives  To compare transvaginal ultrasound measurements of endometrial thickness with direct anatomical measurements and consider the implications of these findings on clinical practice.