Publications

Ovarian endometriosis and infertility: in vitro fertilization (IVF) or surgery as the first approach?

The interval between oocyte retrieval and frozen-thawed blastocyst transfer does not affect the live birth rate and obstetrical outcomes.

BACKGROUND: The 'Freeze all' strategy, which consists of cryopreservation of all embryos after the ovarian stimulation has undergone extensive development in the past decade. The time required for the endometrium to revert to a prestimulation state after ovarian stimulation and thus the optimal time to perform a deferred embryo transfer after the stimulation has not been determined yet. OBJECTIVE: To investigate the impact of the time from oocyte retrieval to frozen-thawed blastocyst transfer (FBT) on live birth rate (LBR), obstetrical and neonatal outcomes, in 'Freeze-all' cycle. MATERIALS AND METHODS: We conducted a large observational cohort study in a tertiary care university hospital including four hundred and seventy-four first autologous FBT performed after ovarian stimulation in 'freeze all' cycles. Reproductive outcomes were compared between FBT performed within the first menstrual cycle after the oocyte retrieval ('cycle 1' group) or delayed FBT ('cycle ≥ 2' group). The main Outcome Measure was the Live birth rate. RESULT(S): A total of 188 FBT were included in the analysis in the 'cycle 1' group and 286 in the 'cycle ≥ 2' group. No significant differences were found between FBT performed within the first menstrual cycle after oocyte retrieval (the 'cycle 1' group) and delayed FBT (the 'cycle ≥ 2' group) in terms of the live birth rate [59/188 (31.38%) vs. 85/286 (29.72%); p = 0.696] and the miscarriage rate [20/82 (24.39%) vs. 37/125 (29.60%), respectively; p = 0.413]. The obstetrical and neonatal outcomes were also not significantly different between the two groups. CONCLUSION: Our study did not detect statistically significant differences in the LBR for FBT performed within the first menstrual cycle after oocyte retrieval versus FBT following subsequent cycles. Embryo-endometrium interaction after a FBT does not appear to be impaired by potential adverse effects of COS whatever the number of cycle between oocyte retrieval and embryo transfer.

Leiomyomatous uterus and preterm birth: an exposed/unexposed monocentric cohort study.

BACKGROUND: The risk of preterm birth may increase in the presence of uterine leiomyomas during pregnancy. Whether myomectomy abrogates this risk has never been studied. OBJECTIVE: Our aim was to evaluate the association between the presence of uterine leiomyomas during pregnancy and preterm birth and, if an association exists, to evaluate its persistence in case of a history of myomectomy. STUDY DESIGN: This exposed/unexposed monocentric retrospective cohort study included all women with singleton pregnancies delivering >22 weeks in a tertiary university hospital maternity unit from January 2011 through September 2015. Women with a leiomyomatous uterus were compared to women with no myomas. Women in the leiomyomatous uterus group were women with uterine leiomyoma(s) during pregnancy (≥1 leiomyoma, measuring ≥20 mm or multiple leiomyomas whatever the size) seen on at least 1 obstetric ultrasound without history of myomectomy, or women with a history of myomectomy (removal of ≥1 leiomyoma, measuring ≥20 mm or multiple leiomyomas whatever the size) by hysteroscopy, laparoscopy, or laparotomy with or without persistent leiomyomas. The association between leiomyomatous uterus and preterm birth was assessed through univariate and multivariable logistic regression. RESULTS: Among the 19,866 women in the cohort, 301 (1.5%) had a leiomyomatous uterus (154 unoperated women and 147 operated women). The rate of premature delivery was 12.0% in the leiomyomatous uterus group and 8.4% in the nonleiomyomatous uterus group. After adjusting for the risk factors for preterm birth, leiomyomatous uterus was significantly associated with preterm birth (adjusted odds ratio, 2.5; 95% confidence interval, 1.7-3.7). This association was significant for unoperated women (adjusted odds ratio, 2.7; 95% confidence interval, 1.6-4.6) as well as operated women (adjusted odds ratio, 2.3; 95% confidence interval, 1.3-3.9) when compared to the nonleiomyomatous uterus group. CONCLUSION: Uterine leiomyomas are associated with preterm birth and this association persists after myomectomy.

Oligo-anovulation is not a rarer feature in women with documented endometriosis.

OBJECTIVE: To study the prevalence of oligo-anovulation in women suffering from endometriosis compared to that of women without endometriosis. DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT (S): We included 354 women with histologically proven endometriosis and 474 women in whom endometriosis was surgically ruled out between 2004 and 2016. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Frequency of oligo-anovulation in women with endometriosis as compared to that prevailing in the disease-free reference group. RESULTS: There was no difference in the rate of oligo-anovulation between women with endometriosis (15.0%) and the reference group (11.2%). Regarding the endometriosis phenotype, oligo-anovulation was reported in 12 (18.2%) superficial peritoneal endometriosis, 12 (10.6%) ovarian endometrioma, and 29 (16.6%) deep infiltrating endometriosis. CONCLUSION(S): Endometriosis should not be discounted in women presenting with oligo-anovulation.

Shedding light on the fertility preservation debate in women with endometriosis: a swot analysis.

Endometriosis, a hormone-dependant condition affecting around 10% of women in their reproductive years, has frequent consequences on fertility. Indeed, a proportion of women will require assisted reproductive techniques or surgery in order to achieve pregnancy. Recent refining of stimulation protocols and vitrification techniques has created new possibilities in the field of fertility preservation. As a consequence, oocyte vitrification is now discussed not only in oncologic situations, but also in other conditions at risk of altered ovarian reserve and poor fertility outcome. In endometriosis, various mechanisms can impair ovarian function and diminish ovarian, particularly bilateral or repeated cystectomy. Fertility preservation could represent an option for women with endometriosis but still remains controversial. In order to shed some light on this complex subject and to outline different issues at stake we conducted a SWOT analysis highlighting strengths, weaknesses, opportunities and threats of oocyte vitrification in women with endometriosis.

Endometriosis and ART: A prior history of surgery for OMA is associated with a poor ovarian response to hyperstimulation.

BACKGROUND: Many women whose fertility may have been impaired by endometriosis require assisted reproductive technology (ART) in order to become pregnant. However, the influence of ovarian endometriosis (OMA) on ovarian responsiveness to hyperstimulation has not been clearly established. OBJECTIVE: To evaluate the risk of a poor ovarian response (POR) to stimulation and ART outcomes in women with OMA. MATERIALS AND METHODS: We conducted a large observational controlled matched cohort study in a tertiary care university hospital between 01/10/2012 and 31/12/2015. After matching by age and anti-Müllerian hormone (AMH) levels, 201 infertile women afflicted with OMA (the OMA group) and 402 disease-free women (the control group) undergoing an ART procedure were included in the study. The main outcomes that we measured were a POR to hyperstimulation (i.e., ≤ 3 oocytes retrieved, or cancelled cycles), the clinical pregnancy rate, and the live birth rate. All of the women with endometriosis underwent a pre-ART work-up, in order to obtain an accurate diagnosis and staging of their disease. An OMA diagnosis was based on published imaging criteria (obtained by transvaginal sonography or magnetic resonance imaging) or on histological analysis for patients with a prior history of endometriosis surgery. The statistical analyses were conducted using univariate and multivariate logistic regression models. RESULTS: The incidence of a POR to hyperstimulation was significantly higher for the OMA group than for the control group [62/201 (30.8%) versus 90/402 (22.3%), respectively; p = 0.02]. However, no significant differences were found between the OMA and the control group in terms of the clinical pregnancy rate [53/151 (35%) versus 134/324 (41.3%), respectively; p = 0.23] and the live birth rate [39/151 (25.8%) versus 99/324 (30.5%), respectively; p = 0.33]. By multivariate analysis, a prior history of surgery for OMA was found to be an independent factor associated with a POR to stimulation [OR = 2.1; 95% CI: 1.1-4.0], unlike OMA without a prior history of surgery [OR: 1.5; 95% CI: 0.9-2.2]. CONCLUSION: The presence of OMA during ART treatment increased the risk of a POR to hyperstimulation, although the live birth rate was not affected. Furthermore, having OMA and having previously undergone surgery for OMA was identified as an independent risk factor for a POR.

Anterior Focal Adenomyosis and Bladder Deep Infiltrating Endometriosis: Is There a Link?

STUDY OBJECTIVE: To evaluate the association between bladder deep infiltrating endometriosis (DIE) and anterior focal adenomyosis of the outer myometrium (aFAOM) diagnosed by preoperative magnetic resonance imaging (MRI). DESIGN: An observational, cross-sectional study using prospectively collected data (Canadian Task Force classification II-2). SETTING: Single university tertiary referral center. PATIENTS: All nonpregnant women younger than 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRI were retained for this study. INTERVENTIONS: Thirty-nine women with histologically proven bladder DIE and an available preoperative MRI were enrolled in the study. Patients were divided into 2 groups: women with aFAOM (aFAOM (+), n = 19) and women without aFAOM (aFAOM (-), n = 20). Both groups were compared for general characteristics, medical history, MRI findings, and disease severity. MEASUREMENTS AND MAIN RESULTS: Nineteen patients (48.7%) with bladder DIE had aFAOM at preoperative MRI. The rate of associated diffuse adenomyosis was similar in the 2 groups (63.2% [n = 12] vs 73.7% [n = 14]; p = .48). The rate of an associated ovarian endometrioma (OMA) was significantly lower in the aFAOM (+) group (10.5% [n = 2] vs 40.0% [n = 8]; p = .03). There were fewer associated intestinal DIE lesions in the aFAOM (+) group compared with the aFAOM (-) group (26.3% vs 75.0%; p = .02), with lower involvement of the pouch of Douglas (26.3% vs 70%; p < .01). Total American Society for Reproductive Medicine score was significantly lower in the aFAOM (+) group (13.8 ± 12.2 vs 62.2 ± 46.2; p < .01). CONCLUSION: aFAOM is present in only half of women with bladder DIE and appears to be associated with lower associated posterior DIE.

Immunology of endometriosis.

The pathophysiology of endometriosis is not completely understood, but an aberrant immune response in the peritoneal environment seems to be crucial for the proliferation of ectopic endometrial cells - as those cells escape apoptosis and peritoneal cavity immunosurveillance. The growth of endometrial implants leads to the recruitment of a large number and diversity of immune cells and intense inflammation with increased pro-inflammatory cytokines, growth factors, and angiogenesis. There is substantial evidence of aberrant function of almost all types of immune cells in women with endometriosis: decreased T cell reactivity and NK cytotoxicity, polyclonal activation of B cells and increased antibody production, increased number and activation of peritoneal macrophages, and changes in inflammatory mediators. New clinical treatments for endometriosis are an urgent need, especially nonhormonal drugs. The study of immunology may clarify its role in the pathogenesis of endometriosis and contribute to the development of new therapeutic strategies.

Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate.

STUDY QUESTION: How does the duration of estrogen (E2) treatment prior to frozen-blastocyst transfers affect the live birth rate (LBR)? SUMMARY ANSWER: Prolonged E2 exposure as part of artificial endometrial preparation (AEP) significantly decreases the LBR after autologous frozen-thawed blastocyst transfer. WHAT IS KNOWN ALREADY: One effective method for endometrial preparation prior to frozen embryo transfer is AEP, a sequential regimen with E2 and progesterone, which aims to mimic the endocrine exposure of the endometrium in a normal cycle. Nevertheless, the optimal duration of E2 administration prior to transfer remains unknown. STUDY DESIGN, SIZE, DURATION: An observational cohort study was conducted in a tertiary care university hospital between 01/07/2012 and 31/12/2015. The main inclusion criteria was having a single frozen-thawed blastocyst transfer with an AEP using exogenous E2. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1377 frozen-thawed blastocyst transfers were assigned to four groups according to the duration of the E2 administration prior to the embryo transfers. These comprised a '≤21 days' group (n = 330), a '22-28 days' group (n = 665), a '29-35 days' group (n = 289) and a '36-48 days' group (n = 93). The '≤21 days' group' was taken as the reference group. The main measured outcome was the LBR following frozen-thawed blastocyst transfers. Statistical analysis was conducted using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: LBR significantly decreased when the E2 exposure prior to the frozen-thawed blastocyst transfer exceeded 28 days: OR = 0.66; 95% CI [0.46-0.95]; P = 0.026 and OR = 0.49 [0.27-0.89]; P = 0.018, respectively, for the '29 to 35 days' group and for the '36 to 48 days' group compared to the reference group. Early pregnancy loss rates significantly increased when the E2 exposure lasted more than 35 days prior to the frozen-thawed blastocyst transfer (OR = 2.37 [1.12-5.05]; P = 0.025 vs. the reference group). After multivariate logistic regression, E2 exposure lasting more than 28 days prior to the frozen-thawed blastocyst transfer was associated with a decrease in the LBR, for the '29-35 days' group (OR = 0.65; [0.45-0.95]; P = 0.044) as for the '36-48 days' group (OR = 0.49; [0.26-0.92]; P = 0.035), vs. the reference group. LIMITATIONS, REASONS FOR CAUTION: One limitation is linked to the observational design of this study. WIDER IMPLICATIONS OF THE FINDINGS: In order to give patients the best chance to obtain a live birth after frozen-thawed blastocyst transfer, the length of E2 exposure prior to the frozen-blastocyst transfer should not exceed 28 days. This study provides new insight in regard to endometrial preparation using AEP prior to frozen-blastocyst transfer. STUDY FUNDING/COMPETING INTEREST(S): No funding and no competing interest.

The definition of Endometriosis Expert Centres.

Endometriosis is a common condition that causes pain and infertility. It can lead to absenteeism and also to multiple surgeries with a consequent risk of impaired fertility, and constitutes a major public health cost. Despite the existence of numerous national and international guidelines, the management of endometriosis remains suboptimal. To address this issue, the French College of Gynaecologists and Obstetricians (CNGOF) and the Society of Gynaecological and Pelvic Surgery (SCGP) convened a committee of experts tasked with defining the criteria for establishing a system of care networks, headed by Expert Centres, covering all of mainland France and its overseas territories. This document sets out the criteria for the designation of Expert Centres. It will serve as a guide for the authorities concerned, to ensure that the means are provided to adequately manage patients with endometriosis.