[Predictive factors of spontaneous pregnancies among women with diminished ovarian reserve patients treated with DHEA]. / Facteurs prédictifs de grossesse spontanée chez les femmes présentant une réserve ovarienne diminuée traitées par DHEA.

INTRODUCTION: Diminished ovarian reserve remains a challenge in the reproductive medicine field. Treatment options for these patients are limited and there is no consensus to make any recommendations. Regarding adjuvant supplements, DHEA could play a role in follicular recruitment and, therefore, may increase spontaneous pregnancy rate. MATERIALS AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme-Mère-Enfant in Lyon. All women presenting with a diminished ovarian reserve treated with 75mg/day of DHEA were consecutively included. The main objective was to evaluate the spontaneous pregnancy rate. The secondary objectives were to identify predictive factors for pregnancy and the evaluation of treatment side effects. RESULTS: Four hundred and thirty-nine women were included. In all, 277 were analyzed, 59 had a spontaneous pregnancy (21.3%). The probability of being pregnant was respectively 13.2% (IC95 9-17.2%), 21.3% (IC95 15.1-27%) and 38.8% (IC95 29.3-48.4%) at 6, 12 and 24 months. Only 20.6% of patients complained of side effects. CONCLUSION: DHEA may improve spontaneous pregnancies in women with diminished ovarian reserve without any stimulation.

Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation.

STUDY QUESTION: What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER: The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY: Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle-Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34-48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26-39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15-26, I2: 0%, fixed-effect) and 33% (95% CI: 25-42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION: The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S): This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER: CRD42021264042.

[Comparison of oral dydrogesterone with micronized vaginal progesterone in fresh embryo transfert in IVF/ICSI]. / Comparaison de la dydrogestérone avec une progestérone micronisée vaginale dans le transfert d'embryon frais en FIV/ICSI.

INTRODUCTION: Luteal insufficiency corresponds to a progesterone deficiency affecting women who receive treatment for in vitro fertilization (IVF). Different routes of progesterone administration exist and have varying degrees of acceptability to patients. The aim of this study was to compare two luteal phase support (LPS) treatments: oral dydrogesterone versus micronized vaginal progesterone on the clinical pregnancy occurrence after fresh embryo transfer. MATERIAL AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme Mère Enfant in Lyon. All the data were collected retrospectively. Women between 18 and 43 years old, who completed an IVF cycle with or without ICSI, followed by fresh embryo transfer on the second or third day after oocyte retrieval (D2 or D3) or at the blastocyst stage (D5 or D6) between July 2019 and July 2020 were included. The 290 patients included between July 2019 and January 2020 received 600mg per day of PMV. The 290 patients in the OD group included between January and July 2020 received 30mg OD per day. RESULTS: In the univariate analysis, the clinical pregnancy occurrence per transfer was comparable between the MVP and OD groups (P>0.05) (OR [95% CI]): 0.904 [0.630 ; 1.296]. In the multivariate analysis, OD also appeared to be associated with a similar pregnancy occurrence compared to MVP, with a non-significant difference (OR [95% CI]): 0.940 [0.640; 1.380]. The use of OD compared to MVP did not significantly influence the clinical pregnancy occurrence in any age group. There was no significant difference between the two groups in the clinical pregnancy occurrence, whether the patients belonged to the reference population of the center or not (P>0.05) (OR [95% CI]): 2.367 [0.568; 3.568]. CONCLUSION: This important French retrospective study confirms the safety and efficacy of OD.

The impact of histones linked to sperm chromatin on embryo development and ART outcome.

The purpose of this study was to investigate the relationship between the proportion of sperm chromatin linked to remaining histone and assisted reproductive technology (ART) outcome. A prospective cohort study was performed on couples undergoing ART process at the Department of Reproduction Medicine (HFME, Bron, France). The histone-to-protamine ratio (HPR) was measured using the method described by Wykes & Krawetz (2003) J Biol Chem 278, 29471. The correlations with sperm DFI, blastocyst formation, pregnancy rate, and delivery rate were investigated. A total of 291 ART cycles were included (42 c-IVF and 249 ICSI procedures): 3870 oocytes were punctured and 2211 embryos were obtained, among which 507 were transferred and 336 frozen. The mean HPR was 18.9%. A significant negative correlation was found between HPR and DFI (r = -0.12, p < 0.05). Regarding the type of ART procedure (c-IVF or ICSI), the same kind of relationship between HPR and ART parameters was observed. Regardless of the type of ART procedure used, when the HPR was within the range [6%; 26%], the blastocyst formation rate was higher: 87.8% vs. 71.2% (HPR<6%; p < 0.01) and 74.6% (HPR >26%; p < 0.01). The highest delivery rate (DR; 24.5%) was obtained for HPR within the range [6%; 26%]; DR was 21.9% for HPR<6% and 18.3% for HPR>26%; however, the differences were not statistically significant. The procedure described in this study seems to be a reliable evaluation of the HPR. The HPR parameter seems to be correlated to embryonic development up to the blastocyst stage, but its involvement in clinical pregnancy/delivery could not be confirmed. HPR should be further investigated for confirming the relationship with blastocyst formation. After this, the next step will be to investigate the etiologies of HPR alterations for improving the sperm nucleus quality for increasing the chance of pregnancy.