Khaled Pocate-Cheriet

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.

A randomized controlled trial comparing the efficacy and safety of two HMG preparations gaining their LH bioactivity from different HCG sources

In this prospective, controlled, randomized, multicentre, non-inferiority study, efficacy and safety of two HMG preparations (Menopur®- Ferring and Meriofert®- IBSA Institut Biochimique SA) for ovarian stimulation were compared (270 women undergoing IVF aged between 18 and 39 years; BMI 30 kg/m2 or less; less than three prior completed assisted reproduction technique cycles). A standard long down-regulation with gonadotrophin-releasing hormone agonist protocol, with HCG triggering was used; primary end-point was total number of oocytes retrieved; attention was paid toovarian hyperstimulation syndrome (OHSS). No statistically significant differences between the treatment groups were reported for most of the clinically significant end-points, including embryo quality, fertilization rate, implantation rate, ongoing pregnancy rate and live birth rate. Total number of oocytes retrieved was higher in the new HMG group compared with the reference (11.6 ± 6.6 and 9.7 ± 5.9, respectively, with a 95% CI of the difference equal +0.43 to +3.43). Increased number of oocytes was obtained through a shorter stimulation, but HMG units per oocyte retrieved were equivalent. The safety profile of the products for frequency of ovarian hyperstimulation syndrome was the same. This study showed that the new HMG preparation is a viable alternative for conducting ovarian stimulation in IVF cycles.

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.

Fertility preservation in women with cancer: a national study about French oncologists awareness, experience, and feelings

PurposeThis study was designed to evaluate patient management and quality of information given by French oncologists to cancer women concerning fertility issues and possibilities of fertility preservation.MethodsAn online survey was sent to 1161 physicians in all major cancer centers throughout France between May 2012 and January 2013.ResultsA total of 102 responses were received and analyzed. Only 46% of all physicians surveyed reported discussing infertility risks with patients of reproductive age and 22% referred them to a fertility center before beginning treatments. Only 14% of practitioners considered themselves knowledgeable in FP techniques and ovarian transposition was the most frequently mentioned technique in consultation.ConclusionThis study is at the best of our knowledge the first nationwide survey to assess the state of the art in oncofertility management. It highlights inadequate management of fertility preservation for female patients in France. Physicians reported lacking knowledge and tools that would allow them to provide patients with appropriate information. A better collaboration between cancer and fertility centers needs to be organized in France as already organized in other countries.