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Study question Do fresh and vitrified/warmed oocytes have the same developmental potential in low prognosis patients defined by POSEIDON criteria? Summary answer Embryos derived from vitrified/warmed oocytes show lower competence for embryo development when compared to those obtained from fresh oocytes in low prognosis patients. What is known already The strategy of oocyte accumulation has been proposed for the management of low-prognosis patients with the aim to increase the number of oocytes available for fertilization and further the number of embryos. The effect of oocyte vitrification/warming on the embryo developmental potential has mainly been studied in oocyte donation programs. Investigations on sibling-oocyte failed to show difference in the morphological embryo development, but the evaluation stopped after 2-3 days of embryo culture. In addition, morphokinetic evaluation revealed delayed development of embryos derived from vitrified oocytes, from the first cleavage to the time of blastulation. Study design, size, duration Single-center sibling-oocyte retrospective monocentric study including low-prognosis patients, defined by POSEIDON criteria, who had undergone an accumulation of oocyte strategy for managing their infertility, between November 2013 and January 2021. Only patients presenting fresh and vitrified/warmed oocytes at the time of insemination were analyzed for the sibling-oocyte comparison. Main study outcomes were fertilization, cleavage, blastulation rates, day-2 and day-5 embryo quality, and the rate of embryos available for transfer/cryopreservation. Participants/materials, setting, methods Forty-five patients were included, with a mean age of 34.8 ± 3.4 years. Oocyte vitrification/warming was performed using the Cryotop method. Top-quality and good-quality embryos were defined at day-2 respectively as 4 and 3-5 adequate-sized blastomeres, without multinucleation and containing Main results and the role of chance A total of 656 oocytes were inseminated, 225 fresh and 431 vitrified/warmed oocytes. The oocyte survival rate after warming was 82%, 95%CI [76-87%]. There was no difference between fresh and vitrified/warmed oocytes groups regarding the degeneration rate following ICSI (5.0% vs 4.8% respectively, p = 0.95), the fertilization rate (74.6% vs 71.4% respectively, p = 0.42) or the cleavage rate on day-2 (98.3% vs 95.4% respectively, p = 0.15). However, the embryo development was significantly different from day 2, with higher day 2 top-quality and good-quality embryos rates in the fresh oocytes group when compared to the vitrified/warmed oocytes group (top-quality: 38.3% vs 24.8% respectively, p = 0.01; good-quality 58.0% vs 45.2% respectively, p = 0.02). The same results were observed on blastocysts when extended culture was decided, with a higher blastulation rate in the fresh oocyte group (56.7% vs 31.7% respectively, p Limitations, reasons for caution The retrospective nature of the study, on a limited number of limited number of patients represents an inherent limitation. Embryo assessment was subjective, the evaluator knowing the oocyte’s source group. The impact of the morphological alterations observed in embryos derived from vitrified/warmed oocytes need to be confirmed with clinical outcomes. Wider implications of the findings The majority of studies comparing fresh and vitrified/warmed oocytes were performed in egg-donation programs. This study focuses on low-prognosis patients, who reflect perhaps more the patients who consult in ART centers. Further prospective studies are needed to confirm our findings. Trial registration number Not applicable

Study question Is IDA-score a useful tool to accurately classify embryos? Summary answer IDA-score is a reliable tool to categorize embryos into top/good/poor morphological quality. However, hierarchical classification of embryos between IDA-score and embryologists was significantly different. What is known already Since Preimplantation Genetic Test for aneuploidy is not authorized in France, morphological scoring by embryologists is the only way to select blastocysts for transfer at Day-5. However, morphological scoring cannot perfectly predict implantation likelihood. Promising recent artificial intelligence techniques might improve both hierarchical classification and clinical outcomes. For instance, IDA-score combined with Embryoscope (Vitrolife®) has been suggested as a way to objectively compare a given embryo to a large embryo dataset and generate a score that predicts the likelihood of implantation using a deep-learning approach. So far, no external independent analysis compares the accuracy of this score with human performance. Study design, size, duration This retrospective-monocentric-study was performed in our reproductive medicine unit from September to December 2021. A total of 167 embryos from 58 couples undergoing ICSI were monitored on a daily-basis and scored at Day-5 by IDA-score and morphological scoring by a panel of senior-embryologists blinded from results of IDA-score. In all, 52 single embryos selected by embryologists were transferred during fresh or frozen cycles. Clinical pregnancy rates were defined by presence of fetal heartbeat on ultrasound. Participants/materials, setting, methods Each embryo was monitored and scored at Day-5 by both morphological scoring and IDA-score. Only the best 3 embryos were ranked and compared. Morphological score was based on Gardner-and-Schoolcraft grading system and classified according to morphological score as top-quality (≥B4BB), good-quality (≥B3BB) and poor-quality ( Main results and the role of chance The mean age of women was 33.96±0.66 years. Morphological scoring led to 68.8% (115/167) top quality embryos, 80.2% (134/167) good quality embryos and 19.8% (33/167) poor quality embryos. Mean IDA-scores of embryos were respectively 9.06 ± 0.48 for top-quality, 8.72 ± 0.62 for good-quality and 7.12 ± 1.34 for poor-quality blastocysts (global p Limitations, reasons for caution These results should be interpreted with caution due to the retrospective design of the study and small effectives. Wider implications of the findings We present preliminary results of an external independent series to confirm the efficiency of IDA-score in daily routine practice. Since IDA-score is not consistent with human scoring concerning hierarchical classification, its performance has to be further assessed to clearly establish the input of artificial intelligence in IVF laboratory practice. Trial registration number not applicable

Study question Does diminished ovarian reserve (DOR) and its etiology impact the AMH/AFC ratio? Summary answer AMH/AFC ratio varies according to the etiology of DOR in young women, suggesting different impact on the follicular health, and further oocyte quality. What is known already Anti-Müllerian hormone and antral follicle count currently represent the two most accurate markers of the follicular ovarian status. Even though they may diagnose a reduction in the follicular stockpile, low values remain inefficient for predicting poor oocyte quality, in particular in young women. Since AMH is produced by the granulosa cells of follicles ranging from primary to small antral follicles, we hypothesized that the etiology of diminished ovarian reserve might differently impact the follicular health and their capacity of producing this peptide. Study design, size, duration From November 2018 to December 2021, we conducted a monocentric, retrospective study including a total of 484 infertile patients < 37 years with DOR. Participants/materials, setting, methods All patients underwent measurement of AMH levels and AFC. DOR was diagnosed according to the Bologna criteria (AMH < 1.1 ng/mL and AFC < 7). AMH/AFC ratio was compared to values obtained in 154 tubal or male infertility patients matched for age and BMI, with AMH and AFC in the normal ranges. This ratio was studied according to the etiology of DOR: genetic (n = 26), post-chemotherapy (n = 102), idiopathic (n = 215) or ovarian diseases (ovarian cyst or history of ovarian surgery, n = 141). Main results and the role of chance Overall, median age of women with DOR was 30 (18-37) years. As expected, age and BMI were comparable in women with DOR and those having normal ovarian reserve tests. In addition, the AMH/AFC ratio failed to show any difference between these 2 groups (0.143 ± 0.22 vs. 0.166 ± 0.11, NS, respectively). Among women with DOR, the etiology was significantly associated with different AMH/AFC ratio. Indeed, patient with DOR of surgical origin (ovarian diseases group) displayed higher mean values (0.283 ± 0.32 ng/mL/ Foll) when compared with those included in genetic (0.079 ± 0.15 ng/mL/ Foll, p Limitations, reasons for caution Despite interesting results, the retrospective nature of the present study may represent a limitation. Moreover, AMH/AFC ratio constitute an indirect method for assessing per follicle AMH production. We hypothesized that this ratio might reflect the follicular health. Its impact on natural conception and assisted reproductive technologies outcome is not known. Wider implications of the findings AMH/AFC ratio may represent an innovative tool aiming to indirectly assess follicular health and possibly oocyte quality in young women with DOR. The etiology of DOR differently impacts the follicular function as reflected by AMH/AFC ratio. Further data on live birth rates following natural or medically assisted pregnancies is needed. Trial registration number N/A

Study question How effective is Assisted Reproduction Technology (ART) in terms of cumulative live birth rate (CLBR) in France, depending on the gonadotropin used? Summary answer Among 214,539 stimulations, originator follitropin-alfa was associated with significantly higher CLBR when compared to Highly Purified-Human Menopausal Gonadotropin (HP-HMG) and biosimilars. What is known already Deciding which type of gonadotropin to prescribe for a woman undergoing controlled ovarian stimulation (COS) remains difficult. The effectiveness of different gonadotropins is one factor to consider. However, studies comparing r-hFSH-alfa, its biosimilars and HP-HMG are scarce and are mostly based on a single ART treatment cycle and fresh embryo transfers. Some clinical trials have shown similar pregnancy, pregnancy loss, and live birth rates after fresh embryo transfer (ET) between HP-HMG and r-hFSH. However, because more oocytes are retrieved with r-hFSH when compared to HP-HMG, it is logical to hypothesize that the CLBR is higher with r-hFSH. Study design, size, duration A non-interventional study based on the French National Health System (SNDS) database was designed to assess the CLBR and treatment costs from the national payer perspective of four gonadotropin groups (originator follitropin-alfa (r-hFSH-alfa), its biosimilars, HP-HMG and r-hFSH-beta) used for COS cycles leading to oocyte pick-up (OPU) between 01/01/2013 and 31/12/2017 with a follow-up period up to 31/12/2018. The study compared CLBR, with originator r-hFSH-alfa as the reference. Participants/materials, setting, methods Women with COS cycles resulting in OPU with one of the specified gonadotropins were included. Data were extracted from billing and reimbursement records of outpatient healthcare consumption and national hospital discharge databases using a unique, anonymized patient number. CLBR was estimated using an Andersen–Gill model, adjusted for clinical baseline, stimulation and ET variables. Costs were reported as secondary outcomes. Main results and the role of chance 135,752 women (mean age 34.1), underwent 214,539 stimulations leading to OPU and contributed one (61.5%), two (24.8%), three (9.4%) or four (3.2%) COS cycles. COS cycles were stimulated with either Originator r-hFSH-alfa (46%), HP-HMG (29%), r-hFSH-beta (21%) or r-hFSH-alfa biosimilars (4%). Over the study period, CLBR reached 20.5%; 21.9% with originator r-hFSH-alfa, 17.9% with HP-HMG, 21.3% with r-hFSH-beta and 18.4% with r-hFSH-alfa biosimilars. After adjusting for age, pre-treatment, GnRH analog, ovulation triggering, luteal phase support, previous COS, fresh or frozen ET and type of center, as possible cofounding variables, the adjusted hazard ratio (HR) for CLBR (delivery [originator r-hFSH-alfa as reference]) was 0.88 (95% CI 0.86 to 0.95, p Limitations, reasons for caution Patients were included only from oocyte pick-up, due to missing data in the SNDS database, meaning that it was not possible to estimate the proportion of cancelled cycles. Furthermore, as r-hFSH-alfa biosimilars were only available since 2015, results for biosimilars should be interpreted with caution. Wider implications of the findings This population-wide French study confirms other Real-World and meta-analysis evidence that CLBR is higher with originator r-hFSH-alfa than with HP-HMG or r-hFSH-alfa biosimilars, respectively, and are relevant for healthcare professionals to support gonadotropin treatment decision making. To further support this, the cost analysis should be completed by a cost-effectiveness analysis. Trial registration number Not applicable

Introduction L’insuffisance ovarienne primitive (IOP) atteint 1 % des femmes avant 40 ans. Un nombre croissant de genes responsables est identifie grâce au sequencage nouvelle generation (NGS). La diminution de la reserve ovarienne (DOR) concerne 10 % des femmes en parcours d’AMP, mais les etiologies sont largement inconnues. Patientes et methodes 70 patientes Caucasiennes de 16–35 ans avec DOR (AMH Resultats et discussion Quatorze patientes (20 %) portent des variants pathogenes (VP) ou probablement pathogenes (VPP) de differentes familles de genes : (1) Reparation de l’ADN : notamment une mutation tronquante de BNC1 et des VPP de ERCC6 dans deux familles non apparentees. Dans l’une d’elle, 2 sœurs ont chacune une IOP ou une DOR confirmant un mecanisme physiopathologique commun. (2) Etablissement du capital folliculaire : notamment SOHLH2 (3) Fonctions mitochondriales notamment POLG, mute dans des IOP avec atteinte neurologique, mais ici remarquablement dans une DOR isolee. Conclusion Ce travail est la premiere etude genetique complete d’une cohorte de DOR. Elle montre (i) la necessite de l’etude genetique des DOR (ii) le lien genetique entre IOP et DOR qui permettrait d’agir sur un plan preventif. Une preservation de la fertilite pourrait etre necessaire chez certaines patientes et leurs apparentees asymptomatiques. (iii) De plus la genetique pourrait apporter des elements importants sur le pronostic de fertilite des DOR.

Resume But Evaluer le taux de grossesses evolutives apres randomisation entre drilling ovarien ou stimulation en cas de resistance au citrate de clomifene (cc). Patientes et methodes Les patientes non enceintes apres 6 a 8 mois de stimulation par cc etaient randomisees : groupe 1, drilling ovarien par fertiloscopie utilisant l’electrochirurgie bipolaire versus groupe 2, metformine 3 mois suivi par 3 cycles avec FSH recombinante associee a une insemination intra-uterine. Le critere d’efficacite est le taux de grossesses evolutives au-dela de 12 semaines. Resultats L’essai therapeutique a du etre arrete apres le screening de 40 patientes. Malgre le faible nombre de patientes incluses, le taux de grossesses est significativement superieur dans le groupe de traitement medical 8/16 versus drilling ovarien 3/18 (p = 0,04). Conclusion Les causes d’echecs de realisation d’un essai therapeutique sont dues aux difficultes mesestimees d’inclusion des patientes en ayant deja eu des stimulations par FSH, a l’absence d’adhesion des equipes a la realisation d’un essai therapeutique, aux difficultes des essais comparant chirurgie et traitement medical faisant preferer aux patientes la prise en charge non chirurgicale. Malgre la faible puissance de l’etude, le traitement medical a ete superieur pour le taux de grossesses observe.

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To evaluate pregnancy rates after randomized controlled trial (RCT) between ovarian drilling by fertiloscopy or ovarian hyperstimulation+insemination+metformine after clomifène citrate (cc) treatment fails.Randomized controlled trial with 126 patients in each arm in 9 university centers. After 6-9 months of stimulation by cc, 2 groups were randomized: group 1, ovarian drilling with bipolar energy versus group 2: 3 months treatment by metformine followed by 3 hyperstimulation by FSH+insemination. The success rate was pregnancy rate above 12 weeks.RCT was stopped after the screening of 40 patients. In spite of the low number of patients, the pregnancy rate is significantly higher in medical group 8/16 versus 3/18 (p=0.04).The causes of fail of RCT were in relationship with difficulties of inclusion, with absence of final agreement by team included. Moreover, RCT between medical and surgical management is often root of difficulties for patients who decline surgical strategy. However, medical treatment appeared better than drilling in this RCT.

Luteinizing hormone (LH) is an hypophyseal glycoprotein involved in both follicular maturation and corpus luteum function. During the follicular phase, effects of LH must be considered according to the stages of follicular development: in the early follicular phase, LH acts through specific receptors, constitutively present on thecal cells, for stimulating androgen production. Androgens seem to be positively involved in the folliculogenesis in primates. Indeed, a positive correlation has been recently established between androgen receptor expression and follicular cell proliferation. Furthermore, androgens are active through a conversion to estrogens in granulosa cells. Estrogens are needed for achieving pregnancy. Thus, a question remains: what in the minimal amount of endogenous LH required for an optimal production of oestradiol? Several models have been investigated in clinical situations with hypogonadotrophic hypogonadism: WHO type I anovulation or GnRH analog-induced hypogonadisms. A large majority of these studies conclude that the minimal amount of LH needed during the follicular phase is probably low (< 1.5 IU/L of plasma LH level). Recent availability of GnRH antagonist will give a new opportunity for evaluating this minimal LH threshold. During the late follicular phase, LH plays a biphasic role, with a positive effect on steroidogenesis but a negative effect on cell proliferation. As suggested by S. Hillier, this negative effect on cell proliferation may be relevant to control the rate of follicular growth. One study, performed in WHO type I anovulatory patients, seems to confirm this assumption but further evaluation is needed to give support to this concept. Finally, LH is also involved in corpus luteum function. Due to the short half-life of LH as compared to hCG, the role of LH must be evaluated according to the adjunct therapies. For example, following a long-term GnRH aganist administration that constantly induces a profound hypophyseal desensitization, LH administration must be repeated to adequately sustain the corpus luteum function. This conclusion must be reconsidered with the recent introduction of GnRH antagonists. Indeed, according to their short-term effects on LH secretion, it may be presumed that a single injection of LH may be effective to maintain an adequate corpus luteum function.

Application of recombinant technology to FSH in the early 1990s produced a highly purified preparation. Calibration of the product was dependent on the rat 'bioassay' based on measurement of ovarian weight after injection of FSH into rats. This test is associated with variability in the measurement of FSH bioactivity (10-20%) and in the batch-to-batch FSH content. To improve calibration of the final product, a new concept of measuring the final product by mass was developed for follitropin alfa, which has a very consistent isoform profile and a high specific activity. The new formulation of follitropin alfa (FbM) displays a very low batch-to-batch variability (< 2%). The advantages of the FbM formulation have been assessed in clinical practice. A significant improvement in the consistency of the ovarian response reported in IVF cycles is likely to be related to the more precise dosing of FbM batches. Similarly, in patients treated for ovulation induction, the cycle cancellation rate was significantly reduced, as well as the need for dose adjustment and repetitive monitoring. Furthermore, the duration of treatment and the total dose of FSH required for cycles with and without IVF were significantly reduced. In conclusion, the new filled-by-mass formulation of follitropin alfa, by providing a more precise dosing of the FSH content in each batch, markedly improves the convenience and effectiveness of stimulation cycles.

To evaluate the benefits, regarding prevention and clinical pregnancy rates, of embryos cryopreservation in patients at high risk of ovarian hyper-stimulation.Retrospective study with 66 patients divided into two groups. Group 1 (n=24), cryopreservation of all the embryos due to high risk of OHSS. Group 2 (n=42), fresh embryo transfer despite of ovarian hyper-response (E24000/mL, hCG day). We performed a comparative analysis for group 1 and 2 regarding implantation, pregnancy, live birth and spontaneous abortion rates.No case of OHSS was observed in group 1 and 40.5 % in group 2. Fresh embryo transfer in group 2 gave the following results: 12.9 % implantation rate, 21.4 % pregnancy rate per transfer and 22.2 % spontaneous abortion. Identical implantation and pregnancy rates after frozen ET cycles were observed in both groups. Whereas live birth rates were significantly better in group 1 (15.4 % vs. 67 %, P=0.04) with a significant lower rate of spontaneous abortion (27 % vs. 11.4 %, P0,01).The negative impact of hyperestrogenic state seems to be limited to endometrial receptivity with no effect on oocyte or embryo quality. In situation of ovarian hyper-response, cryopreservation of all embryos with subsequent transfer of thawed embryos is an efficient strategy to avoid OHSS without decreasing pregnancy and live birth rates.

Miscarriage concerns approximately 15% of pregnancies and recurrent fetal loss (RFL) constitute a particular situation concerning approximately 1% of women. The etiologic inquiry is often disappointing. Nutritional factors represent a promising aspect, insufficiently investigated even if numerous studies underline their impact on fertility, gametogenesis, embryonic development and pregnancies outcome. Obesity is considered as an independent risk factor for miscarriage, involved in oocyte and embryo quality, but also in endometrial receptivity. The male part involved in miscarriage was for a long time underestimated, neglecting the role of sperm in embryo development. If conventional sperm analysis remains essential, new investigations have to be considered such as sperm DNA or oxidant stress evaluation. It is particularly important to take into account nutritional factors as favoring miscarriage because they represent a flexible factor on which intervention is possible to improve pregnancy outcome, with toxics eviction and recommendations for diversified and well-balanced food. At last, effects of nutritional complements for miscarriage prevention remain controversial.

We report a semilobar holoprosencephaly (HPE) in a post-intracytoplasmic-sperm-injection pregnancy. It was suggested by ultrasonography (US), documented on karyotype, identified with magnetic resonance imaging (MRI), established after birth and confirmed on post-mortem autopsy. An amniocentesis revealed a de novo apparently balanced reciprocal translocation 46,XY, t(7;8) (q31.3;q12). Fluorescence in situ hybridization (FISH) identified a deletion in the region of the Sonic Hedgehog gene (SHH) on der(8); nevertheless, the subtelomeric regions for chromosomes 7 and 8 were present. The parents decided to continue the pregnancy; a boy was born and survived for 3 days. The brain autopsy confirmed the semilobar HPE previously noted on US and MRI. Further, band-specific FISH revealed, in addition to SHH deletion, the presence of an inversion in the 7q translocated material on der(8). The parents' karyotypes were normal. An unexpected complex rearrangement was present in a de novo apparently balanced reciprocal translocation in a semilobar HPE.

Evaluer si le diabete gestationnel (DG) est plus frequent et eventuellement associe a un moins bon pronostic apres aide medicale a la procreation (AMP) qu’apres grossesse spontanee. Patientes et methodes Entre 2002 et 2010 chez des femmes sans diabete connu, nous avons analyse les grossesses selon qu’elles etaient spontanees (n = 17 697) ou issues d’AMP (n = 608 : 155 inductions seules, 453 inductions + techniques). Le DG a ete depiste systematiquement. Resultats La plus grande prevalence de DG observee apres AMP versus grossesse spontanee (17,6 vs 14,2 %, p Discussion Independamment des facteurs de confusion, les grossesses apres techniques d’AMP se compliquent plus frequemment de DG. Le pronostic du DG apres AMP apparait cependant bon, peut-etre par le biais d’une meilleure compliance a la prise en charge conseillee.

Ovarian androgen synthesis and regulation are essential to ensure adequate steroidogenesis and folliculogenesis. In primates, there is evidence for a direct impact on the number of small antral follicles and on the process of chronic anovulation. Therefore, serum androgen should be more carefully assessed in infertile women. Accurate measurements of serum androgen are required to better identify patients with androgen excess or deficiency. Medical or surgical interventions are able to decrease ovarian androgen excess and to reduce the risk of hyperstimulation. Conversely, androgen supplementation should be considered in women at risk of low ovarian response to gonadotrophins, related to androgen deficiency. This review supports a specific and broad role of androgen in reproductive physiology.

The success rate of In Vitro Fertilization (IVF) procedure is partly dependent on the ability to transfer embryos within a uterine cavity appropriate for implantation. Indeed, it is has been shown that cervical canal, uterine cavity and endometrial abnomalities may interfer with embryo replacement and implantation [1]. However, the significance of mild intrauterine or cervical pathology is still unknown and the actual incidence of severe abnomalities has been differently appreciated [2,3]. Consequently, the rationale for a systematic evaluation of the uterine cavity is still questionable. To address this issue, we will consider different clinical situations which are usually encountered in our clinical practice and we will discuss the exact place of hysteroscopy which is an useful tool to evaluate uterine cavity [4].

Luteinizing hormone (LH) is an hypophyseal glycoprotein involved in both follicular maturation and corpus luteum function. During the follicular phase, effects of LH must be considered according to the stages of follicular development: in the early follicular phase, LH acts through specific receptors, constitutively present on thecal cells, for stimulating androgen production. Androgens seem to be positively involved in the folliculogenesis in primates. Indeed, a positive correlation has been recently established between androgen receptor expression and follicular cell proliferation. Furthermore, androgens are active through a conversion to estrogens in granulosa cells. Estrogens are needed for achieving pregnancy. Thus, a question remains: what in the minimal amount of endogenous LH required for an optimal production of oestradiol? Several models have been investigated in clinical situations with hypogonadotrophic hypogonadism: WHO type I anovulation or GnRH analog-induced hypogonadisms. A large majority of these studies conclude that the minimal amount of LH needed during the follicular phase is probably low (1.5 IU/L of plasma LH level). Recent availability of GnRH antagonist will give a new opportunity for evaluating this minimal LH threshold. During the late follicular phase, LH plays a biphasic role, with a positive effect on steroidogenesis but a negative effect on cell proliferation. As suggested by S. Hillier, this negative effect on cell proliferation may be relevant to control the rate of follicular growth. One study, performed in WHO type I anovulatory patients, seems to confirm this assumption but further evaluation is needed to give support to this concept. Finally, LH is also involved in corpus luteum function. Due to the short half-life of LH as compared to hCG, the role of LH must be evaluated according to the adjunct therapies. For example, following a long-term GnRH aganist administration that constantly induces a profound hypophyseal desensitization, LH administration must be repeated to adequately sustain the corpus luteum function. This conclusion must be reconsidered with the recent introduction of GnRH antagonists. Indeed, according to their short-term effects on LH secretion, it may be presumed that a single injection of LH may be effective to maintain an adequate corpus luteum function.

Infiltrating leukocyte population appears at the time of implantation in the endometrium of human and other mammals with hemochorial placentation. This leukocyte population is mainly composed of macrophages and typical granular lymphocytes CD56+ CD16-. 63 endometrial samples were studied using immunocytochemistry, before IVF and embryo transfer. We evaluated the sensibility for the assessment of immunological relevant infiltrating cells, of classical histopathologic examination compared with quantitation of leukocyte-common-antigen antibody immunostaining. 21 samples were thoroughly studied during proliferative phase.The sensibility of classical histologic analysis for the semi-quantitative assessment of leukocyte population, even when performed by an experienced histopathologist, is only 62%. When leukocyte population during proliferative phase is dense, it is mainly composed of macrophages and CD56+ CD16- lymphocytes.Immunological reaction already reported around the time of implantation may occur at other period of the menstrual cycle. Close mechanisms of the control and functions of this characteristic reaction remain to clarify.

During hMG therapy for ovarian stimulation, the common criteria used to appreciate both follicular growth and granulosa cells maturity are the simultaneous determination of plasma oestradiol levels and ultrasound measurement of the size of the follicles. However such an approach does not take into account that, when administered at pharmacological doses, hMG stimulate the growth of secondary and tertiary follicules and therefore create an extraphysiological hormonal environment. Although the rate of growth is identical between the follicles stimulated by hMG, their development is initiated at different periods of time during the follicular phase. For that reason, it is usual to observe a degree of asynergy in the size and maturation of the different follicles. Moreover, from IVF practice, it becomes evident that, in cycles stimulated by hMG, a dissociation between granulosa cells and oocyte maturation may be present and decreases the predictive value of the hormonal index of granulosa cell maturation. In fact, if the role of the hormones on the follicular growth and on the granulosa cells differentiation is well understood, their implication on growth and meiotic competence of the oocyte is still unknown, at last in human beings.