Mathilde Bourdon

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.

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.

Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes

STUDY QUESTION What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? SUMMARY ANSWER Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE, DURATION This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014. 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 MRIs were retained for this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Surgery was performed on 292 patients with signed consent and available preoperative MRIs. After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group. The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n = 292). Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%), associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8 cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3 cases); P < 0.001). FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3% (110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery. Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis. This could explain the high number of women with DIE (166/237-70%) in our study group. This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis. Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women. This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group. Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown. WIDER IMPLICATIONS OF THE FINDINGS This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis. Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S) No funding supported this study. The authors have no 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.

The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: A retrospective matched cohort study

Background Controlled ovarian stimulation in assisted reproduction technology (ART) may alters endometrial receptivity by an advancement of endometrial development. Recently, technical improvements in vitrification make deferred frozen-thawed embryo transfer (Def-ET) a feasible alternative to fresh embryo transfer (ET). In endometriosis-related infertility the eutopic endometrium is abnormal and its functional alterations are seen as likely to alter the quality of endometrial receptivity. One question in the endometriosis ART-management is to know whether Def-ET could restore optimal receptivity in endometriosis-affected women leading to increase in pregnancy rates. Objective To compare cumulative ART-outcomes between fresh versus Def-ET in endometriosis-infertile women. Materials and methods This matched cohort study compared def-ET strategy to fresh ET strategy between 01/10/2012 and 31/12/2014. One hundred and thirty-five endometriosis-affected women with a scheduled def-ET cycle and 424 endometriosis-affected women with a scheduled fresh ET cycle were eligible for matching. Matching criteria were: age, number of prior ART cycles, and endometriosis phenotype. Statistical analyses were conducted using univariable and multivariable logistic regression models. Results 135 in the fresh ET group and 135 in the def-ET group were included in the analysis. The cumulative clinical pregnancy rate was significantly increased in the def-ET group compared to the fresh ET group [58 (43%) vs. 40 (29.6%), p = 0.047]. The cumulative ongoing pregnancy rate was 34.8% (n = 47) and 17.8% (n = 24) respectively in the Def-ET and the fresh-ET groups (p = 0.005). After multivariable conditional logistic regression analysis, Def-ET was associated with a significant increase in the cumulative ongoing pregnancy rate as compared to fresh ET (OR = 1.76, CI95% 1.06–2.92, p = 0.028). Conclusion Def-ET in endometriosis-affected women was associated with significantly higher cumulative ongoing pregnancy rates. Our preliminary results suggest that Def-ET for endometriosis-affected women is an attractive option that could increase their ART success rates. Future studies, with a randomized design, should be conducted to further confirm those results.

Live birth rate following frozen–thawed blastocyst transfer is higher with blastocysts expanded on Day 5 than on Day 6

STUDY QUESTION The aim of this study was to evaluate the live birth rate (LBR) after frozen-thawed Day 5 (D5) and Day 6 (D6) blastocyst transfers. SUMMARY ANSWER LBR following frozen-thawed blastocyst transfer is significantly lower with D6 than with D5 blastocyst regardless of embryo quality. WHAT IS KNOWN ALREADY During fresh embryo transfer cycles, pregnancy rates (PR) are significantly higher when transferring blastocysts expanded on D5 compared with slow developing blastocysts (D6). In programmed thawed blastocyst transfer (TBT) cycles, the same clinical outcomes should be expected when transferring D5 or D6 blastocysts because of endometrial/embryonic synchronization due to hormonal priming of endometrial receptivity. However, the impact of delayed blastocyst expansion at D6 on clinical outcomes remains unclear. Some reports have shown higher PRs after D5 TBT compared with those of D6, while others have shown equivalent TBT outcomes after D5 and D6 cryopreserved blastocysts transfers. STUDY, DESIGN, SIZE, DURATION This retrospective cohort follow-up study included 1347 single autologous frozen-thawed blastocyst transfers performed between January 2012 and December 2015 at a tertiary care university hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS All of the patients scheduled for TBT were allocated to two groups according to the day of blastocyst expansion: on D5 (n = 994) or on D6 (n = 353). The primary outcome was LBR per embryo transfer in the first blastocyst thawing cycle. Secondary outcomes were clinical pregnancy rate (cPR), early miscarriage rate and neonatal outcomes following TBT for the two groups. Statistical analyses were conducted using univariate and multivariate logistic regression model. MAIN RESULTS AND THE ROLE OF CHANCE The LBR was significantly increased in the D5 group compared to the D6 group [294/994 (29.6%) versus 60/353 (17.0%); P < 0.001]. The cPR was also higher when blastocysts were vitrified on D5 compared with those vitrified on D6 [429/994 (43.2%) versus 95/353 (26.9%); P < 0.001]. No significant differences were found between groups in terms of early miscarriage rate (P = 0.862). More good-quality embryos (defined as an B3-B4 or B5 embryo ≥BB according to the grading scale proposed by Gardner) were transferred in the D5 group than in the D6 group [807 (81.2%) versus 214 (60.6%); P < 0.001]. However, a comparison of TBT cycles with equal embryo quality (good versus low) also supported the superiority of D5 blastocysts. Concerning neonatal outcomes, the D5 group infants had a lower mean birth weight compared to those of the D6 group (P = 0.001). In addition, a significantly shorter gestational age at birth is reported in the D5 blastocyst group as compared to the D6 group (P = 0.004). After multivariate logistic regression taking into account potential confounders such as the womens age, number of previous IVF/ICSI procedures, the day of the blastocyst vitrification (D5 or D6) and embryo quality, blastocyst expansion at D6 was independently associated with a significant decrease in LBR compared to D5 expanded-blastocysts (OR 0.52; 95% CI 0.38-0.72; P < 0.001). LIMITATIONS, REASONS FOR CAUTION The poor predictive value of the morphological approach in embryo selection could constitute a limitation in this study. However, blastocyst quality was evaluated similarly in both groups. WIDER IMPLICATIONS OF THE FINDINGS The LBR following frozen-thawed blastocyst transfer was significantly lower with D6 than with D5 blastocysts, regardless of their quality. These results could affect cryopreservation procedures as they suggest that the use of D5-expanded blastocysts for TBT may be preferred in order to shorten the time of conceiving. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained for this study. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable.

Traitement conservateur des endométriomes chez les patientes prises en charge en FIV

Endometriosis is a chronic disease. The pathogenesis is actually still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical). Among the different phenotypes of endometriosis, the ovarian endometrioma seems to most important lesion in the management of endometriosis-related infertility. Surgical treatment is associated to a decrease of the ovarian reserve and a potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the choice between conservative or surgical management of endometrioma before IVF is actually debated. The advantages and drawback of surgical and conservative management should be discussed before to plan the treatment. In the present review, we aimed at assessing the risks of a conservative management of endometrioma as compared to surgery before IVF.

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.

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.