[Endometriosis Fertility Index, or classification of the American Society of Reproductive Medicine for postoperative endometriosis patients with infertility: Which is more relevant?]. / Endometriosis Fertility Index ou classification de l'American Society of Reproductive Medicine pour les patientes infertiles endométriosiques opérées. Lequel est le plus pertinent ?

The revised American Fertility Society classification system has been most used after surgery by all consensus on endometriosis fertility. However, it does not predict pregnancy. The EFI score has been recently developed to aim at predicting clinical pregnancy after surgery. Several study performed its external validation. It may be a useful new tool to counsel couples for personalized postoperative management.

[Laparoscopy in ART?]. / Y a-t-il une place pour la cœlioscopie dans le parcours en assistance médicale à la procréation ?

The use of laparoscopy in infertility is currently controversial. However, laparoscopic treatment of tubal and peritoneal disease, or endometriosis improves natural fecundity and ART results. The use of laparoscopy in unexplained infertility can be considered because of underestimated pelvic pathology. The result of laparoscopy may help the practitioner for choosing spontaneous pregnancy or ART postoperative management. Although there is a lack of randomized study, laparoscopy is useful for a high overall pregnancy rate (surgery and ART treatment). Rather than opposing ART and laparoscopy, the integrated approach seems better for personal management.

Delivery rates after elective single cryopreserved embryo transfer related to embryo survival.

OBJECTIVE: The objective of this study was to assess if eSCET (elective Single Cryopreserved Embryo Transfer) outcome is related to blastomere survival rate. The final objective was to avoid multiple pregnancies and offer the best chances to women to achieve pregnancy even during their frozen-thawed embryo transfer (FET) cycles. STUDY DESIGN: Patients were included in this prospective observational study if they met the following criteria: (i) women age <37 years old; (ii) IVF of ICSI cycle rank ≤2, (iii) eSET proposed during fresh embryo transfer cycle and (iv) ≥1 good quality cryopreserved embryos available (<20% fragmentation and 4-5 blastomeres at day-2 or 7-9 blastomeres at day-3). Live birth rates (LBR) were compared into eSCET groups according to embryo survival (partially damaged or intact transferred embryo). RESULTS: We observed among selected patients, that partial loss of blastomeres (1 blastomere for day-2 embryos, 1 or 2 blastomeres for day-3 embryos) following FET cycles did not affect LBR compared with intact embryo. CONCLUSION: These results underline the relevance of eSCET as a strategy to reduce multiple pregnancies frequency without reducing LBR.

[Unilateral borderline ovarian tumor and unilateral adenexectomy?]. / Tumeur limite de l'ovaire unilatérale : l'annexectomie est-elle le bon choix ?

To perform an adnexectomy in case of unilateral borderline tumor must consider the risk of recurrence, the preservation of fertility, and to integrate a global comprehensive management of a couple. Adnexectomy can be considering as a legitimate option when the woman desire a pregnancy. The risk of recurrence is low and the global survey high. Identification of woman with a high risk of recurrence is necessary. Adnexectomy can be considering as a legitimate option to preserve fertility in case of unilateral tumor. However, ovarian reserve data are missing after the surgery. Adnexectomy can be considering for the management of infertile woman with unilateral borderline tumor. IVF can be performed in the absence of any poor prognosis factor. Management with ovarian cryopreservation and In vitro Maturation remain unclear.

[48,XXYY men with azoospermia: how to manage infertility?]. / Azoospermie et tétrasomie 48,XXYY : quelle prise en charge de l'infertilité ?

48,XXYY syndrome is a rare form of sex chromosomal aneuploidy. Usually considered as a variant of Klinefelter syndrome because of shared features (azoospermia, tall stature, hypergonadotropic hypogonadism), it is a separate entity because diagnostic is currently made in prepubertal boy with neuro-psychological disorders. We here report the case of a 48,XXYY patient consulting for adult infertility and the indication to perform testicular sperm extraction is discussed.

[Varicocele and infertility: where do we stand in 2013?]. / Varicocèle et infertilité: où en sommes-nous en 2013?

While the incidence of clinical varicocele is common in infertile men (about 40%), the reasons why varicocele may affect sperm parameters is still unclear. In addition, the improvement of fertility after treatment of varicocele is also a subject of debate. The purpose of this review is to get new insight into the physiopathology of varicocele, its impact on sperm parameters and the effectiveness of varicocele treatment on fertility. Treatment is likely to be effective in infertile men with clinical varicocele and impaired spermatogenesis. Even if it does not systematically lead to an improvement in sperm parameters, it may prevent further sperm degradation. In case of non-obstructive azoospermia, few studies reported a slight improvement in the process of spermatogenesis. The critical role of an adequate methodology in order to establish clinical guidelines needs to be stressed. Indeed, the huge intra-individual variability in sperm production makes the usual analysis of sperm parameters inadequate to measure treatment effectiveness. Regarding the assessment of conception, it requires not only well designed and properly sized studies but also a multivariate analysis for weighing predictive factors of success. Thus, an active scientific research is needed to better identify pathogenic agents and appropriately assess the impact of varicocele treatment.

[Elective cryopreservation of all embryos in women at risk of ovarian hyperstimulation syndrome: prevention and efficiency]. / Cryopréservation de la cohorte embryonnaire en cas de risque d'hyperstimulation: prévention et efficacité.

OBJECTIVE: To evaluate the benefits, regarding prevention and clinical pregnancy rates, of embryos cryopreservation in patients at high risk of ovarian hyper-stimulation. PATIENTS AND METHODS: 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 (E2>4000/mL, hCG day). We performed a comparative analysis for group 1 and 2 regarding implantation, pregnancy, live birth and spontaneous abortion rates. RESULTS: 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 %, P<0,01). DISCUSSION AND CONCLUSION: 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.

[Outcome of embryo vitrification compared to slow freezing process at early cleavage stages. Report of the first French birth]. / Issue de la vitrification des embryons précoces versus congélation lente. Rapport de la première naissance française.

OBJECTIVES: Since the end of 2010, France by "l'Agence de Biomédecine" has validated the embryo vitrification procedure as an improvement of the slow freezing method. We presented here data concerning biological and clinical outcomes from a prospective observational study where early cleavage stage good quality embryos were vitrified and warmed. We compared these results to those of a retrospective series where embryos were thawed after a slow freezing procedure (SF). We report also the first French live birth following embryo vitrification. PATIENTS AND METHODS: In all, 58 cycles of frozen-thawed embryo transfers (FET) following vitrification were prospectively included and compared with 189 FET from SF method. Primary end points were the (i) survival rate (SR) (% of embryos with ≥50% post-thaw intact blastomeres), (ii) intact survival rate (ISR) (% of embryos with 100% post-thaw intact blastomeres) and (iii) survival blastomeres index (SBI) (% of post thaw intact blastomeres per survival embryo). Secondary end point was the clinical pregnancy rate (CPR) defined as the presence of an intra-uterine gestational sac with positive foetal heart beat. We report here the first French live birth following embryo vitrification. RESULTS: In all, 87 and 412 embryos have been thawed following vitrification and SF, respectively. We observed a highly significant increase of SR, ISR et SBI respectively when thawing concerned vitrified embryos rather than those from SF method (98.3±13.1% vs. 77.3±32.0%, P<10(-4); 88.2±28.3% vs. 47.7±41.4%, P<10(-4); 97.7±6.1% vs. 87.3±14.4%, P<10(-4)). Furthermore, CPR were of 32.7% (19/58) and of 18.5% (35/189) following FET performed after vitrification or SF and thawing (P=0.03), respectively. The live birth of two healthy girls occurred following a caesarean section after 38 weeks of amenorrhea the 8th of August 2011. DISCUSSION AND CONCLUSION: We experienced in our study that the post-thaw survival of vitrified embryos was significantly better than those of embryos resulting from SF. Then, a better CPR per thawed embryo cycle was observed following vitrification.

Impact of 'LH activity' supplementation on serum progesterone levels during controlled ovarian stimulation: a systematic review.

BACKGROUND: The influence of LH on serum progesterone rise during gonadotrophin stimulation is a matter of debate. The purpose of this analysis was to assess the impact of supplementation with 'LH activity' products on serum progesterone changes before hCG administration in GnRH analog-treated women. METHODS: A computerized literature search was performed to identify studies comparing FSH treatment alone to those that provided supplementation with 'LH activity' using hMG, recombinant (r)LH (rLH) or hCG in GnRH analog protocols. Data regarding stimulation regimens were extracted from those that reported serum progesterone levels at the time of hCG in order to assess the specific role of LH activity products. RESULTS: Serum progesterone determination at the time of hCG administration was performed in 34 out of 108 studies comparing the effects of FSH alone or in combination with LH activity products. In a vast majority, no significant difference in serum progesterone could be found between stimulation regimens. However, in four studies where LH activity (three hMG and one rLH) was administered from the beginning of ovarian stimulation, serum P-values were significantly decreased. In contrast, in two studies where LH activity (hCG) was provided during the late follicular phase, serum P-values were significantly increased. Analysis of confounding factors showed that the intensity of ovarian stimulation is the most important determining factor to explain serum progesterone elevation at the time of hCG administration, CONCLUSIONS: This systematic review shows that providing LH activity supplementation in combination with FSH during ovarian stimulation does not have a consistent effect on serum progesterone concentrations at the time of hCG administration. However, these data also suggest that, in accordance with physiological concept, the timing of LH activity administration could influence the impact on serum progesterone changes.

[Fertility after endometrial osseous metaplasia elective hysteroscopic resection]. / Fertilité après résection élective hystéroscopique de lésions de métaplasie ostéoïde de l'endomètre.

OBJECTIVES: The endometrial osseous metaplasia is a rare disease which is characterized by the presence of osseous tissue in endometrium. It is often diagnosed in women with secondary infertility. The main objective of this work is to evaluate fertility after elective resection of osteoid metaplasia endometrial lesions by operative hysteroscopy in infertile women. PATIENTS AND METHOD: Retrospective and descriptive series of 7 cases observed in the Woman and Child department, CHU Jean-Verdier. The 7 women were in reproductive age, of African origin, with secondary infertility after abortions concerning 6 out of the 7 patients. RESULTS: In all cases, endovaginal pelvic ultrasound has raised endometrial calcification, and diagnostic hysteroscopy highlighted endometrial osteoid metaplasia. The operative hysteroscopic procedure consisted of elective diathermic resection to handle endometrial insertion of bone chips. A second diagnostic hysteroscopy was systematically done. It showed no recurrence. Six of the 7 patients began pregnancy, 3 spontaneously and 3 after IVF/ICSI in the first year following the hysteroscopic treatment. The evolution of pregnancies has been marked by 2 normal deliveries, 1 spontaneous miscarriage and then an ectopic pregnancy in one patient, 1 growth retardation intrauterine requiring caesarean at 38 SA, 1 HELLP syndrome in a twin pregnancy requiring ceasarean at 27 SA followed normal labor at term and 1 pregnancy lost sight. DISCUSSION AND CONCLUSION: Hysteroscopic elective resection seems to be the treatment of choice with a good prognosis on subsequent fertility.

Polycystic ovary syndrome (PCOS).

1. The Rotterdam classification should be used to define PCOS in the event of: menstrual cycle anomalies; amenorrhoea, oligomenorrhoea or long cycles, clinical and/or biochemical hyperandrogenism and ultrasound appearance of polycystic ovaries. 2. The presence of two of these three criteria is sufficient once all other diagnoses have been ruled out. 3. Diagnosis of hirsutism should not be based on the Ferriman-Gallway score. 4. The ultrasound definition of PCOS contains precise criteria that must be included in the report: presence of at least 12 follicles in each ovary measuring 2-9 mm in diameter, and/or increase in ovary size>10 ml. 5. Screening for elevated plasma LH no longer necessary. Testing for GnRH serves no purpose. 6. Routine screening for metabolic abnormalities should be carried out systematically based on weight, height and BMI, waist circumference, blood pressure and laboratory parameters: plasma glucose, triglycerides, HDL cholesterol. 7. In the case of obesity (BMI>30 kg/m(2)), oral glucose tolerance testing (OGTT) is recommended where fasting serum glucose is normal. 8. Clomiphene citrate (CC) remains the first-line therapy for ovulation induction. In patients with BMI>30, it should be preceded by improvement of metabolic status through appropriate lifestyle modifications.

[Views of each member of an Assisted Reproductive Technologies centre on the embryo transfer procedure]. / Points de vue de l'équipe multidisciplinaire d'un centre d'Assistance médicale à la procréation concernant le transfert embryonnaire.

The embryo transfer (ET) is probably the key step of Assisted Reproductive Technologies (ART), end point of the collaboration of a multidisciplinary clinical team and an infertile couple. Thus, a perfect knowledge of available data regarding ET is required to optimize the results of ART. Indeed, numerous published studies demonstrate the impact of defined parameters onto the effectiveness of ET procedure. The aim of this study is to provide views of physicians dealing with ART, i.e. endocrinologist, ultrasound scan specialist, surgeon and biologist to put in perspective questions and answers about ET.

Short gamete co-incubation during in vitro fertilization decreases the fertilization rate and does not improve embryo quality: a prospective auto controlled study.

PURPOSE: Evaluate the effect of short gamete incubation on fertilization rate and embryo quality. METHODS: A prospective study has been performed. Two thousand five hundred and forty seven sibling oocytes from 240 couples undergoing IVF attempts were allocated to a short (1 h) or a standard (18 h) insemination procedure. Diploid fertilization rate (two pronuclei, 2PN), polyspermy (>2PN) and embryo quality were compared. RESULTS: The fertilization rate was statistically lower in the short insemination group compared to the standard insemination one (64.9% and 70.1%; P = 0.039), with a similar polyspermy rate observed between the two groups. A slight, but non significant, increase was observed concerning good embryo quality rate in the short insemination group when compared to the standard insemination, both at day 2 (60.1 vs. 58.1%; P = 0.06) and day 3 (53.2 vs. 48.5%; P = 0.22). CONCLUSION: This new study highlights that a 1 h gamete exposure decreases the fertilization rate and does not improve embryo quality compared with a standard 18 h insemination procedure.

[The use of GnRH antagonists in ovarian stimulation for intrauterine inseminations: is there any interest?]. / Utilisation des antagonistes de la GnRH au cours des stimulations pour inséminations intra-utérines: y a-t-il un intérêt?

The use of the GnRH antagonists during ovarian stimulation for intrauterine insemination is relatively recent. The primary aim was to improve the timing of the inseminations on working days. However, according to published data, the consequences on pregnancy rate remain uncertain. Moreover, the impact of this strategy on stimulation's parameters, specifically on the size of the follicle cohort, should be better assessed.

[Prospective evaluation of elective single-embryo transfer versus double-embryo transfer following in vitro fertilization: a two-year French hospital experience]. / Evaluation prospective du transfert sélectif d'un embryon: deux années d'expérience.

OBJECTIVE: Multiple embryo transfer is responsible for a high rate of multiple pregnancies (ICSI), with subsequent risks of premature birth and perinatal death. This prospective non randomized study aimed to assess the ability of an elective single-embryo transfer (eSET) policy to reduce the twin pregnancy rate, compared to a double embryo transfer (DET) approach. PATIENTS AND METHODS: Between March 2005 and May 2006, 180 eligible women were proposed to benefit from an eSET transfer rather than a DET. Inclusion criteria were (i) age less than 37 years old; (ii) at least two good quality embryos available (three to five cells at day 2 or six to nine cells at day 3; less than 20% fragmentation and the absence of multinucleates blastomeres), after IVF or ICSI and (iii) no more than one previous failed treatment cycle. Outcome analysis included cycles with frozen-thawed embryo transfer (FET). RESULTS: According to patients' decision, 107 and 73 women had an eSET (59.4%) and a DET (40.6%) respectively. No differences were found between eSET and DET groups regarding demographics and biologicals parameters. The clinical pregnancy rate (PR) per transfer was 43.9% in eSET group and 57.5% in DET group (p=0.07). The twin pregnancy rates were 0 and 14.3%, in eSET and DET groups, respectively (p=0.007). The cumulative PR per patient, including the outcome of performed FET cycles, was 63.6% in eSET group and 61.6% in DET group. In this case, the cumulative twin pregnancy rates were 2.9 and 15.6% in eSET and DET groups, respectively (p=0.02). DISCUSSION AND CONCLUSION: Our data show that in a selected population of women, transferring one fresh embryo and then, if required, one or two frozen-thawed embryos significantly reduces the twin pregnancy rate without decreasing the overall pregnancy rate. This study supports the policy of eSET in this subgroup of patients.

Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation.

BACKGROUND: The role of LH in sensitizing antral follicles to FSH is unclear. LH is required for normal hormone production and normal oocyte and embryo development, but follicular responses to LH may depend upon the stage of development. Potential roles at the early follicular phase were explored in a clinical setting by employing a sequential approach to stimulation by recombinant human (r-h) LH followed by r-hFSH in women who were profoundly down-regulated by depo GnRH agonist. METHODS: We employed a multi-centre, prospective, randomized approach. Women (n = 146) were treated in a long course high-dose GnRH agonist (Decapeptyl, 4.2 mg s.c.) protocol and were randomized to receive r-hLH (Luveris, 300 IU/day) for a fixed 7 days, or no r-hLH treatment. This was followed by a standard r-hFSH stimulation regime (Gonal-F, 150 IU/day). Ultrasound and hormone assessments of responses were measured at the start of r-hLH treatment, on FSH stimulation Days 0 and 8 and at the time of HCG administration. RESULTS: The LH treatment was associated with increased small antral follicles prior to FSH stimulation (P = 0.007), and an increased yield of normally fertilized (2 PN) embryos (P = 0.03). There was no influence of the r-hLH pretreatment upon hormone profiles or ultrasound assessments during the FSH phase. Anti-mullerian hormone increased in both groups during the week prior to FSH stimulation (P = 0.002). CONCLUSIONS: This sequential approach to the use of r-hLH in standard IVF showed a possible modest clinical benefit. The results support other recent work exploring up-regulated androgen drive upon follicular metabolism indicating that clinical benefit may be obtainable after further practical explorations of the concept.

[Follicle-stimulating hormone receptor polymorphism and ovarian function]. / Polymorphisme du gène du récepteur de la FSH et fonction ovarienne.

The FSH receptor presents several polymorphisms. Two of them, located at codon 307 and 680, are the most frequent. Threonine can be substituted by alanine at position 307 and serine can be substituted by asparagine at position 680. The two most frequent allelic combinations are Thr(307) -Asn (680) (60%) and Ala(307) -Ser (680) (40%). As the allelic variants at codon 307 and 680 are almost invariably associated, most of the studies assessed only one codon (680) and classified the women as homozygous (Ser/Ser ou Asn/Asn) or heterozygous (Asn/Ser). Several studies aimed to correlate the follicle-stimulating hormone receptor polymorphism and ovarian function. Women homozygous for the Ser (680) variant have higher follicular FSH levels and longer follicular phase length, which suggest a lower sensitivity to FSH. The FSH receptor genotype would also influence the sensitivity to exogenous FSH: as regards ovarian stimulation, higher recombinant FSH doses are needed for Ser/Ser homozygous women. The analysis of polymorphism in women with premature ovarian failure did not show a link with any particular allelic variant. In women with polycystic ovaries, the distribution of the allelic variants greatly varies from one study to another.

[Hypothyroidism: from the desire for pregnancy to delivery]. / Hypothyroïdie: du désir de grossesse à l'accouchement.

The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.