Vanessa Gayet

In women with endometriosis anti-Müllerian hormone levels are decreased only in those with previous endometrioma surgery

STUDY QUESTION Are anti-Müllerian hormone (AMH) levels lower in women with endometriosis, notably those with endometriomas (OMAs) and deep infiltrating lesions, compared with controls without endometriosis? SUMMARY ANSWER Endometriosis and OMAs per se do not result in lower AMH levels. AMH levels are decreased in women with previous OMA surgery independently of the presence of current OMAs. WHAT IS KNOWN ALREADY The impact of endometriosis and OMAs per se on the ovarian reserve is controversial. Most previous studies have been conducted in infertile women. The strength of our study lies in the following points: (i) the selection of women undergoing surgery and not only according to the presence of infertility, (ii) the classification of women with endometriosis and controls based on strict surgical and histological criteria. STUDY DESIGN, SIZE, DURATION Cross-sectional study using data prospectively collected in all non-pregnant <42-year-old patients, who were surgically explored for a benign gynaecological condition at a university tertiary referral centre between 2004 and 2008. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. AMH levels were measured in serum samples drawn in the month preceding surgery, without regard to menstrual phase or hormonal therapy. PARTICIPANTS/MATERIALS, SETTING, METHODS Operations were done on 1262 women between 2004 and 2008, of which 1133 signed the informed consent. Of the 566 women with a visual diagnosis of endometriosis, 411 had histologically proven endometriosis. Frozen serum samples for the AMH measurement were available in 313 of them. Out of the 554 women without visual endometriosis and without past endometriosis surgery, 413 had a frozen serum sample for the AMH measurement. Univariate analysis examined AMH levels according to baseline patient characteristics, the presence and type of endometriosis (superficial lesion, OMA, deep infiltrating lesion) and previous OMA surgery. Analysis of variance-covariance then examined the effects of co-variables on AMH levels. Finally, logistic regressions were conducted to examine the odds ratio (OR) of having AMH levels <1 ng/ml according to the same co-variables. MAIN RESULTS AND THE ROLE OF CHANCE The difference in AMH levels between women with endometriosis and controls did not reach significance (3.6 ± 3.1 versus 4.1 ± 3.4 ng/ml, P = 0.06). Analysis of variance-covariance demonstrated that AMH levels significantly decreased with age (P < 0.001) and in women with prior OMA surgery irrespective of whether OMAs were present or not at the time of study (P < 0.05). Logistic regression revealed that two major factors were related to AMH levels <1 ng/ml: (i) age (compared with <29 years; 30-34 years OR = 3.1, 95% CI: 1.5-6.4, P = 0.01; 35-39 years OR = 7.0, 95% CI: 3.5-14.1, P = 0.001; ≥40 years OR = 20.8, 95% CI: 9.1-47.4, P = 0.001) and (ii) prior OMA surgery (OR = 3.0, 95% CI: 1.4-6.41, P = 0.01). LIMITATIONS, REASONS FOR CAUTION The selection of our study population was based on a surgical diagnosis. Women with an asymptomatic form of endometriosis are therefore not included in our study. We cannot exclude that infertile women with OMAs associated with a diminished ovarian reserve, as assessed during their infertility work-up, were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that OMAs per se do not diminish the ovarian reserve reflected by AMH levels but that alterations seen in women with endometriosis are a deleterious consequence of OMA surgery. These findings should be taken into account in the decision to operate OMAs in women with a desire for future pregnancy. STUDY FUNDING/COMPETING INTERESTS STUDY FUNDING none. Potential competing interests: none.

HIV-positive patients undertaking ART have longer infertility histories than age-matched control subjects

OBJECTIVE To review 5 years of assisted reproductive treatments (ART) provided to couples affected by human immunodeficiency virus (HIV). DESIGN Age-matched cohort study. SETTING University-based tertiary center. PATIENT(S) Couples in whom the male (n = 87), female (n = 57), or both (n = 17) partners were HIV infected. The first ART cycle was compared with three sets of age-matched control subjects (3-to-1) which included 261, 171, and 51 couples, respectively. INTERVENTION(S) ART in HIV-infected couples and age-matched controls. MAIN OUTCOME MEASURE(S) Infertility duration and ART outcome. RESULT(S) When initiating ART, all three HIV-infected groups had longer infertility histories, computed from when conception was attempted or infertility diagnosed, compared with noninfected age-matched control subjects. Outcome, however, was not different when only the male or female partner was infected, though with a trend toward higher cancellation and lower pregnancy rates. When both partners were HIV infected, cancellation were higher and pregnancy rates lower (12% versus 41.2%), than in age-matched control subjects. CONCLUSION(S) Our data showed longer infertility histories in all HIV-infected couples when undertaking their first ART. Outcome, however, was not altered when only one partner--male or female--was HIV infected. Efforts should therefore aim at assuring that HIV-infected couples access ART as promptly as their noninfected counterparts.

Endometriosis-related infertility: assisted reproductive technology has no adverse impact on pain or quality-of-life scores

OBJECTIVE To evaluate the impact of assisted reproduction technology (ART) on painful symptoms and quality of life (QoL) in women who have endometriosis as compared with disease-free women. DESIGN Prospective controlled, observational cohort study. SETTING University hospital. PATIENT(S) Two hundred and sixty-four matched-pairs of endometriosis and disease-free women undergoing ART. INTERVENTION(S) Assessment of pain evolution using visual analogue scale (VAS) during ART; QoL assessment with the Fertility Quality of Life (FertiQoL) tool. MAIN OUTCOME MEASURE(S) VAS pain intensities relative to dysmenorrhea, dyspareunia, noncyclic chronic pelvic pain (NCCPP), gastrointestinal pain, lower urinary tract pain; trends for VAS change between postretrieval and baseline evaluation; FertiQoL score; and statistical analyses conducted using univariate and adjusted multiple linear regression models. RESULT(S) After excluding canceled cycles and patients lost to follow-up observation, 102 women with endometriosis and 104 disease-free women were retained for the study. The trends for VAS change between the postretrieval and baseline evaluations in the women with endometriosis compared with the disease-free women revealed a statistically significant pain decrease for dysmenorrhea (-1.35 ± 3.23 and 0.61 ± 4.00) and dyspareunia (-1.19 ± 2.58 and 0.14 ± 2.06). For NCCPP, gastrointestinal symptoms, and lower urinary tract symptoms, there were no statistically significant differences between the groups. After multiple linear regression, no worsening of pain was observed in the endometriosis group as compared with disease-free group. In addition subgroup analysis according to endometriosis phenotype failed to show any increase of pain. The quality of life in the endometriosis group was comparable to that of the disease-free group. CONCLUSION(S) Assisted reproduction technology did not exacerbate the symptoms of endometriosis or negatively impact QoL in women with endometriosis as compared with disease-free women.

Retrieving oocytes from small non-stimulated follicles in polycystic ovary syndrome (PCOS): in vitro maturation (IVM) is not indicated in the new GnRH antagonist era

It has been two decades since pregnancies have been obtained through in vitro maturation (IVM) of germinal vesicle-stage oocytes retrieved from non-stimulated ovaries. This technique first offered in PCOS cannot be recommended today in this indication because the results do not match those of regular ART, and new GnRH antagonist and agonist-trigger protocols reliably prevent OHSS.

Prognostic factors for assisted reproductive technology in women with endometriosis-related infertility

Background: Assisted reproductive technology is one of the therapeutic options offered for managing endometriosis‐associated infertility. Yet, published data on assisted reproductive technology outcome in women affected by endometriosis are conflicting and the determinant factors for pregnancy chances unclear. Objective: We sought to evaluate assisted reproductive technology outcomes in a series of 359 endometriosis patients, to identify prognostic factors and determine if there is an impact of the endometriosis phenotype. Study Design: This was a retrospective observational cohort study, including 359 consecutive endometriosis patients undergoing in vitro fertilization or intracytoplasmic sperm injection, from June 2005 through February 2013 at a university hospital. Endometriotic lesions were classified into 3 phenotypes–superficial peritoneal endometriosis, endometrioma, or deep infiltrating endometriosis–based on imaging criteria (transvaginal ultrasound, magnetic resonance imaging); histological proof confirmed the diagnosis in women with a history of surgery for endometriosis. Main outcome measures were clinical pregnancy rates and live birth rates per cycle and per embryo transfer. Prognostic factors of assisted reproductive technology outcome were identified by comparing women who became pregnant and those who did not, using univariate and adjusted multiple logistic regression models. Results: In all, 359 endometriosis patients underwent 720 assisted reproductive technology cycles. In all, 158 (44%) patients became pregnant, and 114 (31.8%) had a live birth. The clinical pregnancy rate and the live birth rate per embryo transfer were 36.4% and 22.8%, respectively. The endometriosis phenotype (superficial endometriosis, endometrioma, or deep infiltrating endometriosis) had no impact on assisted reproductive technology outcomes. After multivariate analysis, history of surgery for endometriosis (odds ratio, 0.14; 95% confidence ratio, 0.06–0.38) or past surgery for endometrioma (odds ratio, 0.39; 95% confidence ratio, 0.18–0.84) were independent factors associated with lower pregnancy rates. Anti‐müllerian hormone levels <2 ng/mL (odds ratio, 0.51; 95% confidence ratio, 0.28–0.91) and antral follicle count <10 (odds ratio, 0.27; 95% confidence ratio, 0.14–0.53) were also associated with negative assisted reproductive technology outcomes. Conclusion: The endometriosis phenotype seems to have no impact on assisted reproductive technology results. An altered ovarian reserve and a previous surgery for endometriosis and/or endometrioma are associated with decreased pregnancy rates.

Increased rate of spontaneous miscarriages in endometriosis-affected women

STUDY QUESTION Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. WHAT IS KNOWN ALREADY The association between endometriosis and miscarriages has long been debated without reaching a consensus. STUDY DESIGN, SIZE, DURATION We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). MAIN RESULTS AND THE ROLE OF CHANCE Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16). LIMITATIONS, REASONS FOR CAUTION There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. STUDY FUNDING/COMPETING INTERESTS No external funding was used for this study. The authors have no conflicts of interest to declare.

Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited

Ovarian stimulation improves assisted reproductive technology outcome by increasing the number of oocytes available for insemination and in-vitro handling. A recent Duplex protocol features a dual stimulation, with the second stimulation started immediately after the first oocyte retrieval. Remarkably, the Duplex protocol is unexpectadly well tolerated by women and provides twice as many oocytes and embryos as a regular antagonist protocol in less than 30 days.

Impaired sperm motility in HIV-infected men: an unexpected adverse effect of efavirenz?

STUDY QUESTION Are antiretroviral therapies associated with semen alterations in HIV-infected men? SUMMARY ANSWER Antiretroviral regimens that included the non-nucleosidic reverse transcriptase inhibitor efavirenz were associated with a significant impairment of sperm motility, whereas regimens without efavirenz were not associated with significant semen changes. WHAT IS KNOWN ALREADY Semen alterations including decreased ejaculate volume and sperm motility have been reported in HIV-infected men. The hypothesis ascribing reduced sperm motility to damages induced in sperm mitochondria by nucleosidic (or nucleotidic) reverse transcriptase inhibitors (NRTIs) has not been confirmed in HIV-infected patients and the effects of antiretroviral treatments on semen parameters remain unclear. STUDY DESIGN, SIZE, DURATION This case-control study compared semen characteristics across 378 HIV-1 infected patients receiving different antiretroviral regimens or never treated by antiretroviral drugs, in whom an initial semen analysis was done between 2001 and 2007. PARTICIPANTS/MATERIALS, SETTING, METHODS The patients were partners from serodiscordant couples requesting medical assistance to procreate safely. Their status with regard to antiretroviral therapy at the time of semen analysis was categorized as follows: 1/ never treated patients (n = 66); 2/ patients receiving NRTIs only (n = 49); 3/ patients receiving a NRTIs + protease inhibitor (PI) regimen (n = 144); 4/ patients receiving a NRTIs + non-nucleosidic reverse transcriptase inhibitor (NNRTI) regimen (n = 119). Semen parameters were assessed through standard semen analysis. Additional analyses included measurement of sperm motion parameters using computer-assisted semen analysis, seminal bacteriological analysis, seminal biochemical markers and testosterone plasmatic levels. All analyses were performed in the Cochin academic hospital. The data were analyzed through multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE Sperm motility was the only semen parameter which significantly varied according to treatment status. The median percentage of rapid spermatozoa was 5% in the group of patients receiving a regimen including efavirenz versus 20% in the other groups (P < 0.0001). Accordingly, sperm velocity was reduced by about 30% in this group (P < 0.0001). The role of chance was minimized by the strict definition and the size of the study population, which included a large enough group of never treated patients, the controlled conditions of semen collection and analysis, the multivariate analysis, the specificity and the high significance level of the observed differences. LIMITATIONS, REASONS FOR CAUTION The design of the study did not allow demonstrating a causal link between exposure to efavirenz and sperm motility. WIDER IMPLICATIONS OF THE FINDINGS As efavirenz is widely used in current antiretroviral therapy, these findings may concern many HIV-infected men wishing to have children. This justifies further assessment of the consequences on fertility of the exposure to efavirenz. Moreover, the possibility of common cellular impacts underlying adverse effects of efavirenz in sperm cells and neurons deserved investigation. STUDY FUNDING/COMPETING INTERESTS No external funding was used for this study. None of the authors has any conflict of interest to declare.

Does GnRH Agonist Triggering Control Painful Symptom Scores During Assisted Reproductive Technology? A Retrospective Study.

Objective: The aim of this study was to assess the progression of pain symptoms during assisted reproductive technology (ART) cycles following administration of GnRH agonist (GnRHa) versus human chorionic gonadotrophin (hCG) triggering. Design: Observational cohort study. Setting: A tertiary care university hospital in France. Population: Patients who underwent ART programs. Methods: Between January 01, 2014, and June 31, 2014, 122 cycles were allocated to 2 groups: GnRHa triggering with a scheduled differed embryo transfer (n = 57) or hCG triggering with a fresh embryo transfer (n = 70). Pelvic pain scores were evaluated using a visual analog scale (VAS) with regard to dysmenorrhea, dyspareunia, noncyclic pelvic pain, gastrointestinal, and lower urinary tract pain. The total VAS score was defined as the sum of the scores for the various symptoms. Evaluations were carried out twice: during the synchronization treatment prior to ovarian stimulation and during a final evaluation 3 weeks postretrieval. The data were processed using univariate and multivariate logistic regression models. Main Outcome Measures: Trends for total VAS change (ie, final VAS score − synchronization VAS score). Results: For both groups, pain increased during the ART procedure. Trends for the total VAS change revealed that the increase in pain was significantly less in the “GnRHa triggering” group compared to the “hCG triggering” group (3.77 ± 7.73 and 6.50 ± 6.57, P < .05, respectively). Multivariate logistic regression indicated that GnRHa triggering was associated with less of an increase in pain compared to hCG triggering (odds ratio = 0.31, 95% confidence interval 0.13-0.71, P < .05). Conclusion: Compared to hCG, GnRHa triggering limits pain symptom progression in the period immediately after ART.

Deferred frozen embryo transfer: what benefits can be expected from this strategy in patients with and without endometriosis?

Progress with cryopreservation techniques have enabled development of the deferred frozen-thawed embryo transfer (DET) strategy as an alternative to relying on fresh embryo transfers. With DET, the entire embryo cohort is cryopreserved, and embryo transfer is then performed in a subsequent cycle that takes place separately from the controlled ovarian stimulation (COS). Initially developed to limit the risk of ovarian hyperstimulation syndrome that occurs with high responders, this strategy has been applied extensively with other populations in an effort to improve implantation rates. The assumption is that COS, which is essential for in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) procedures to obtain a multi-follicular development, could have a detrimental impact on the endometrium as a result of greatly elevated levels of steroids. It is currently not clear whether the DET strategy can be generally applied to all women requiring an IVF/ICSI procedure. The objectives of this literature review regarding DET, were hence: (i) to present the scientific background that contributed to extensive adoption of this technique, (ii) to detail the pregnancy outcomes and potential obstetric and neonatal consequences, (iii) to report on its ability to prevent risks induced by COS, and (iv) to propose indications for the DET strategy in clinical practice.