What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs?

BACKGROUND: Endometriosis is commonly observed in infertile women and can be staged with regard to severity [e.g. according to the American Fertility Society (AFS) classification]. This condition can cause infertility through impaired oocyte quality, fertilization disorders, tubal lesions, adhesions, deep infiltration, and adenomyosis. Although women with endometriosis often turn to in vitro fertilization (IVF) programs, the literature data on IVF outcomes are sometimes contradictory (i.e. the same as in other etiologies of infertility, or worse). The objective of the present study was to assess and compare pregnancy rates in women with and without endometriosis and according to the endometriosis stage. METHODS: We retrospectively studied clinical and ongoing pregnancy rates in IVF and the cumulative pregnancy rates after frozen/thawed embryo transfers, in women without endometriosis (group A) or with endometriosis (group B). We further compared groups in which endometriosis was staged according to the revised AFS classification: stage 1/2 (group C), stage 3/4 (group D, without endometrioma), and endometrioma alone (group E). RESULTS: We documented 430 cycles in group A and 460 in group B (including 56 in group C, 88 in group D and 316 in group E). After fresh or frozen/thawed embryo transfers, the differences in ongoing pregnancy rates between groups A and B were not significant. However the cumulative rates per couple were significantly lower (p < 0.05) in group D. CONCLUSIONS: We recommend IVF for women with endometriosis because the pregnancy rates are similar to those observed for women with other types of infertility. This approach is in line with the international guidelines issued by assisted reproductive technology societies. These results again raise the question of whether surgical resection of deep infiltrating endometriosis (stage 3/4) should be recommended before admission to an IVF program. Trial registration This study was approved by an institutional review board (CPP Ouest VI, Brest, France): reference: B2020CE.43.

Live Birth Rates in Women Under 38 Years Old with AMH Level < 1.2 ng/ml in the First In Vitro Fertilization + / - Intracytoplasmic Sperm Injection: Retrospective Study and Arguments for Care.

Many studies failed to show a predictive impact of AMH levels on the chances of pregnancy; however, acceptable pregnancy rates for young women with low AMH levels were observed in IVF + / - ICSI. The objectives of this retrospective study were to evaluate the clinical pregnancy and live birth rates in the first IVF + / - ICSI cycle in women under 38 years old with AMH level < 1.2 ng/ml and to determine the arguments for care. We classified the women into three groups: group A: AMH < 0.4 ng/ml (n: 86); group B: AMH: 0.4 to 0.8 ng/ml (n: 90); and group C: AMH > 0.8 to < 1.2 ng/ml (n: 92). We recorded data on the patients' characteristics, stimulation cycles, embryo cultures, and ongoing pregnancies. No difference was observed between the three groups for the number of embryos transferred, the clinical pregnancy, and the live birth rates (LBR) per embryo transfer (LBR/transfer: 24.1% in group A, 25.9% in group B, and 28.1% in group C). The young age of the women reassures about the oocyte quality, but a low level of AMH may raise concerns about a lower quantitative oocyte yield, leading to accelerated management of the couple in IVF + / - ICSI.

Should intrauterine inseminations still be proposed in cases of unexplained infertility? Retrospective study and literature review.

OBJECTIVE: Unexplained infertility is defined by the absence of identifiable causes of infertility. The results of randomized studies and meta-analysis regarding the treatment of unexplained infertility are discordant due to methodological problems. DESIGN: The aim of this study is to compare the clinical pregnancy rate per cycle (CPR/c) in IUI and IVF/ICSI in cases of unexplained infertility, according to the woman's age group and to identify the factors which predict success. INTERVENTIONS: We performed a retrospective study in two ART centers, comparing overall clinical pregnancy, ongoing pregnancy and live birth rates in IVF/ICSI and IUI. We also compared pregnancy and birth rates according to different female age groups. RESULTS: 855 IVF/ICSI and 804 IUI cycles were compared. We found a significant difference (p < 0.001) in the pregnancy and live birth rates per cycle between IUI and IVF/ICSI, overall and in the different female age groups, except in women aged 40 and over. The greatest chances of pregnancy with IUI are found in women with secondary unexplained infertility, during the first two cycles and with a bi-follicular response to stimulation. In IVF/ICSI, pregnancy rates are higher in women with secondary unexplained infertility, in the first two cycles, in IVF and in women receiving a transfer of two embryos regardless of the embryonic stage. CONCLUSION: We recommend IVF/ICSI treatment rather than IUI for unexplained infertility (OR CPR/c 4.20 with 95% CI [3.72-4.68]). This is in accordance with NICE, which advises the use of IVF after 2 years.

MACS-annexin V cell sorting of semen samples with high TUNEL values decreases the concentration of cells with abnormal chromosomal content: a pilot study.

We question whether, in men with an abnormal rate of sperm DNA fragmentation, the magnetic-activated cell sorting (MACS) could select spermatozoa with lower rates of DNA fragmentation as well as spermatozoa with unbalanced chromosome content. Cryopreserved spermatozoa from six males were separated into nonapoptotic and apoptotic populations. We determined the percentages of spermatozoa with (i) externalization of phosphatidylserine (EPS) by annexin V-Fluorescein isothiocyanate (FITC) labeling, (ii) DNA fragmentation by TdT-mediated-dUTP nick-end labeling (TUNEL), and (iii) numerical abnormalities for chromosomes X, Y, 13, 18, and 21 by fluorescence in situ hybridization (FISH), on the whole ejaculate and selected spermatozoa in the same patient. Compared to the nonapoptotic fraction, the apoptotic fraction statistically showed a higher number of spermatozoa with EPS, with DNA fragmentation, and with numerical chromosomal abnormalities. Compared to the whole ejaculate, we found a significant decrease in the percentage of spermatozoa with EPS and decrease tendencies of the DNA fragmentation rate and the sum of disomy levels in the nonapoptotic fraction. Conversely, we observed statistically significant higher rates of these three parameters in the apoptotic fraction. MACS may help to select spermatozoa with lower rates of DNA fragmentation and unbalanced chromosome content in men with abnormal rates of sperm DNA fragmentation.

Fertility preservation and sperm donation in transgender individuals: The current situation within the French CECOS network.

BACKGROUND: Many studies reported that reproductive desire could be high among transgender individuals. In France, fertility preservation and sperm donation were very little proposed to transgender individuals until recently, mainly because the Bioethics Law allows the use of assisted reproductive technologies only in infertile couples and prohibits surrogacy. OBJECTIVES: To evaluate the distribution of care on the French territory concerning fertility preservation and sperm donation in transgender individuals. MATERIALS AND METHODS: A multicentric national survey was carried out between January 2019 and October 2020 in 28 assisted reproductive technology centres of the French CECOS (Centres d'Etudes et de Conservation des Oeufs et du Sperme) network. Each centre was questioned to find out how many transgender individuals came, were informed and cared for fertility preservation and sperm donation. RESULTS: Concerning fertility preservation, 71.4% of centres received transgender individuals and performed gamete cryopreservation; 581 transgender individuals consulted for fertility preservation. Transgender women were more likely to desire (p < 0.0001) and achieve (p < 0.0001) fertility preservation than transgender men. Concerning sperm donation in couples including a transgender man, 68% of centres offer the complete course from the first consultation to the completion of the assisted reproductive technology cycles; 122 offsprings have been conceived with sperm donation in couples including a transgender man since 1999. DISCUSSION: Our results showed that even if all centres do not propose fertility preservation or sperm donation in transgender individuals, these assisted reproductive technologies are present throughout the French territory. The major point is that both fertility preservation and sperm donation in transgender individuals have grown significantly and that the care of these patients is improving year after year. CONCLUSION: In France, most of CECOS centres can take care of transgender individuals for fertility preservation and sperm donation. The French Bioethics Law allows these latter, and transgender individuals can benefit from a financial support of the national health care insurance for fertility preservation and sperm donation.

Can Ratios Between Prognostic Factors Predict the Clinical Pregnancy Rate in an IVF/ICSI Program with a GnRH Agonist-FSH/hMG Protocol? An Assessment of 2421 Embryo Transfers, and a Review of the Literature.

None of the models developed in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is sufficiently good predictors of pregnancy. The aim of this study was to determine whether ratios between prognostic factors could predict the clinical pregnancy rate in IVF/ICSI. We analyzed IVF/ICSI cycles (based on long GnRH agonist-FSH protocols) at two ART centers (the second to validate externally the data). The ratios studied were (i) the total FSH dose divided by the serum estradiol level on the hCG trigger day, (ii) the total FSH dose divided by the number of mature oocytes, (iii) the serum estradiol level on the trigger day divided by the number of mature oocytes, (iv) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day, (v) the serum estradiol level on the trigger day divided by the number of mature oocytes and then by the number of grade 1 or 2 embryos obtained, and (vi) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day and then by the number of grade 1 or 2 embryos obtained. The analysis covered 2421 IVF/ICSI cycles with an embryo transfer, leading to 753 clinical pregnancies (31.1% per transfer). Four ratios were significantly predictive in both centers; their discriminant power remained moderate (area under the receiver operating characteristic curve between 0.574 and 0.610). In contrast, the models' calibration was excellent (coefficients: 0.943-0.978; p < 0.001). Our ratios were no better than existing models in IVF/ICSI programs. In fact, a strongly discriminant predictive model will be probably never be obtained, given the many factors that influence the occurrence of a pregnancy.

Comparison of human embryomorphokinetic parameters in sequential or global culture media.

A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.

[Assisted oocyte activation: a new tool for severe male factor infertility treatment]. / Aide à l'activation ovocytaire - Un nouvel atout dans le traitement des infertilités masculines sévères.

In severe male infertility, in vitro fertilization (IVF) with intra-cytoplasmic sperm injection (ICSI) represents the sole available therapeutic option. However this technique is not always successful in promoting fertilization, as some couples completely and repeatedly fail to obtain any embryo. In many cases, this failure can be attributed to a defective rise in intracellular calcium, which is required to achieve oocyte activation. Over the last twenty years, several laboratories dedicated to assisted reproduction technologies have been using a calcium ionophore to assist oocyte activation. The aim of this review is to give an overview of the advances and consequences associated with this new technique referred to as assisted oocyte activation.