rFSH in medically assisted procreation: Evidence for ovarian follicular hyperplasia and interest of mass spectrometry to measure 17-hydroxyprogesterone and Δ4-androstenedione in serum.

Ovarian monitoring requires the determination of serum estradiol and progesterone levels. We investigated whole follicular steroidogenesis under rFSH in medically assisted procreation (MAP: 26 IVF, 24 ICSI) compared to 11 controls (IUI). Estrone, estradiol, Δ4-androstenedione, testosterone, progesterone and 17-hydroxyprogesterone were measured by immunoassay and mass spectrometry except for estrogens. At the start of a spontaneous or induced cycle, steroids levels fluctuated within normal ranges: estradiol (314-585 pmol/L), estrone (165-379 pmol/L) testosterone (1.3-1.6 nmol/L), Δ4-androstenedione (4.5-5.6 nmol/L), 17-hydroxyprogesterone (2.1-2.2 nmol/L) and progesterone (1.8-1.9 nmol/L). 17-hydroxyprogesterone, Δ 4-androstenedione and estradiol predominated. Then estradiol and oestrone levels rise, but less markedly for oestrone in IUI. In MAP, rFSH injections induce a sharp increase in estrogens associated with a rise in 17-hydroxyprogesterone and Δ4-androstenedione levels, disrupting oestrogen/androgen ratios. rFSH stimulation induces an ovarian hyperplasia and Δ4pathway which could become abnormal. Determining 17-hydroxyprogesterone and Δ4-androstenedione levels with LC-MS/MS may therefore be useful in managing recurrent MAP failures.

[Ovarian hyperstimulation syndrome after stimulation with highly purified hMGfor in vitro fertilization: Observational study SHOview]. / Le syndrome d'hyperstimulation ovarienne après stimulation par hMG hautement purifiée dans le cadre de la fécondation in vitro : étude observationnelle SHOview.

OBJECTIVE: Data on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in France are limited. METHODS: Prospective observational multicentric study (23 French centers of IVF) in a cohort of 421 women treated with highly purified hMG (HP-hMG) for the first or second cycle of IVF with or without ICSI. The primary objective was to assess the incidence of moderate to severe OHSS in this cohort. RESULTS: At inclusion, 172 patients (40.9%) were considered at risk of OHSS by the physicians. The main measures for risk minimization taken by the physicians rested on initial dose of HP-hMG and protocol choice. At the end of the follow-up (4 months in average), the rate of OHSS moderate to severe was 2.4% (confidence interval 95%: 1.1-4.3%) for the studied IVF cycle. OHSS was severe for 3 women (0.7%) and moderate for 7 women (1.7%). CONCLUSION: This rate of OHSS after IVF is at the lower limit of the rates reported in the literature for OHSS. This study brings reassuring epidemiological data on the rate of OHSS in women at risk. The measures taken by the physicians to minimize the risk of OHSS could have contributed to this low incidence.

[Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for oocyte donors]. / Valeurs comparées de la corifollitropine alpha et de la FSH quotidienne dans la stimulation ovarienne des donneuses d'ovocytes.

OBJECTIVES: To demonstrate that corifollitropin alfa is as effective as daily FSH in controlled ovarian stimulation of oocyte donors. METHODS: From January 2013 to October 2015, 77 cycles controlled ovarian stimulation, derived from a continuous cohort of 77 oocyte donors, were analyzed. After synchronization by oestroprogestatif or estrogens, ovarian stimulation was started by corifollitropin alfa (Group corifollitropin alfa) or by daily FSH (Group daily FSH). In both groups, a GnRH antagonist was used for the prevention of premature surge of luteinizing hormone (LH). The induction of ovulation was induced by a GnRH agonist. The duration of treatment, estradiol rate, numbers of mature oocytes, fertilization rate, clinical and ongoing pregnancies rates were evaluated in the two groups. RESULTS: There is no difference for the age, the markers of ovarian reserve and the duration of treatment. The average rate of estradiol on the eighth day of the stimulation is lower for the corifollitropin alfa (845±694.5 vs 1742±1177.3, P<0.001), there is no difference in the number of mature oocytes retrieved (14.4 vs 13.4, P=0.979), with a fertilization rate significantly higher in the corifollitropin alfa group (59.8% vs 49.3%, P<0.001). The rate of ongoing pregnancies is higher but without reaching significant difference in this same group (36.6% vs 26%, P=0.277). CONCLUSION: As compared to daily FSH, corifollitropin alfa, in oocyte donors offers, advantages in terms of ease of use with identical efficiency.

[Conservative management of endometrioma in women undergoing in vitro fertilization]. / Traitement conservateur des endométriomes chez les patientes prises en charge en FIV.

Endometriosis is a chronic disease. The pathogenesis is actually still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical). Among the different phenotypes of endometriosis, the ovarian endometrioma seems to most important lesion in the management of endometriosis-related infertility. Surgical treatment is associated to a decrease of the ovarian reserve and a potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the choice between conservative or surgical management of endometrioma before IVF is actually debated. The advantages and drawback of surgical and conservative management should be discussed before to plan the treatment. In the present review, we aimed at assessing the risks of a conservative management of endometrioma as compared to surgery before IVF.

Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation for infertility.

STUDY QUESTION: Is there an association between the endometriosis phenotype and presentation with infertility? SUMMARY ANSWER: In a population of operated patients with histologically proven endometriosis, ovarian endometrioma (OMA) per se is not associated with an increased risk of presentation with infertility, while previous surgery for endometriosis was identified as a risk factor for infertility. WHAT IS KNOWN ALREADY: The increased prevalence of endometriosis among subfertile women indicates that endometriosis impairs reproduction for reasons that are not completely understood. STUDY DESIGN, SIZE, DURATION: This was an observational, cross-sectional study using data prospectively collected in all non-pregnant patients aged between 18 and 42 years, who were surgically explored for benign gynaecological conditions at our institution between January 2004 and March 2013. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed in 2208 patients, of which 2066 signed their informed consent. Of the 1059 women with a visual diagnosis of endometriosis, 870 had histologically proven endometriosis and complete treatment for their endometriotic lesions, including 307 who presented with infertility. Univariate analysis and multiple logistic regression analysis were performed to determine factors associated with infertility. MAIN RESULTS AND THE ROLE OF CHANCE: The following variables were identified as risk factors for endometriosis-related infertility: age >32 years (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.4), previous surgery for endometriosis (OR = 1.9; 95% CI: 1.3-2.2), as well as peritoneal superficial endometriosis (OR = 3.1; 95% CI: 1.9-4.9); Conversely, previous pregnancy was associated with a lower rate of infertility (OR = 0.7; 95% CI: 0.6-0.9 and OR = 0.6; 95% CI: 0.4-0.9, respectively). OMA is not selected as a significant risk factor for infertility. LIMITATIONS, REASON FOR CAUTION: The selection of our study population was based on a surgical diagnosis. We cannot exclude that infertile women with OMA associated with a diminished ovarian reserve, as assessed during their infertility work-up, were referred less frequently to surgery and might therefore be underrepresented. In addition we cannot exclude that our group of infertile women present associated other causes of infertility. WIDER IMPLICATIONS OF THE FINDINGS: Identification of risk and preventive factors of endometriosis-related infertility can help improve clinical and surgical management of endometriosis in the setting of infertility. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: None.

[Risk of perinatal complication and egg donation: Role of resorting to cross-border care?] / Les risques périnataux sont-ils plus importants après don d'ovocytes à l'étranger ?

OBJECTIVES: In France, egg donation is covered by Social insurance among women<43 years old. Because of shortage of egg donor, women aged 43 years or more cannot resort to egg donation in French infertility centers, leading them to turn to the foreign centers having practices different and less regulated than in France. We are thus brought to take care of the pregnancy and of the delivery of these women. Our objective was to estimate if the perinatal risks are more important after egg donation abroad than in case of egg donation in a French center. MATERIAL AND METHODS: Retrospective study between January, 2010 and April, 2013, comparing women having had an egg donation to Cochin then having delivered in the maternity hospital of their choice (n=88) and the women having had an egg donation abroad then having delivered in the Port-Royal maternity (n=121). First, the modalities of egg donation were compared between the Cochin hospital and the foreign centers. Second, the obstetric and perinatal outcomes were compared between both groups, then by stratifying according to the type of pregnancy (singleton or multiple). RESULTS: Among women having had an egg donation abroad, the age of the donor was lower (25.7 vs. 31.7, P=0.001), the average number of embryos transferred higher (2.1±0.6 vs. 1.7±0.5, P=0.001) and the rate of multiple pregnancies higher (47.9% vs. 9.1%, P=0.001) than among women having had an egg donation at Cochin. We observed after egg donation abroad compared to egg donation at Cochin, a birth weight significantly lower (2678±745g vs. 3045±682g, P=0.001) and a prevalence of intrauterine growth retardation higher (11.1% vs. 4.2%, P=0.04). Among singletons, abnormal placentation was more frequent in case of egg donation abroad (17.5% vs. 5.1%, P=0.02). In case of twin pregnancy, we highlighted very high rates of complications, without significant difference according to the place where egg donation was practiced. CONCLUSION: We observed an increased risk of intrauterine growth retardation after egg donation abroad, which could essentially be explained by the association between advanced maternal age and multiple gestation. For other obstetric and perinatal complications, the differences between both groups were less important than expected, but very high in both groups, whether the egg donation was realized in France or abroad. The complications seem mainly due to the multiple gestations, justifying the transfer of a single embryo whenever possible.

Impaired sperm motility in HIV-infected men: an unexpected adverse effect of efavirenz?

STUDY QUESTION: Are antiretroviral therapies associated with semen alterations in HIV-infected men? SUMMARY ANSWER: Antiretroviral regimens that included the non-nucleosidic reverse transcriptase inhibitor efavirenz were associated with a significant impairment of sperm motility, whereas regimens without efavirenz were not associated with significant semen changes. WHAT IS KNOWN ALREADY: Semen alterations including decreased ejaculate volume and sperm motility have been reported in HIV-infected men. The hypothesis ascribing reduced sperm motility to damages induced in sperm mitochondria by nucleosidic (or nucleotidic) reverse transcriptase inhibitors (NRTIs) has not been confirmed in HIV-infected patients and the effects of antiretroviral treatments on semen parameters remain unclear. STUDY DESIGN, SIZE, DURATION: This case-control study compared semen characteristics across 378 HIV-1 infected patients receiving different antiretroviral regimens or never treated by antiretroviral drugs, in whom an initial semen analysis was done between 2001 and 2007. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients were partners from serodiscordant couples requesting medical assistance to procreate safely. Their status with regard to antiretroviral therapy at the time of semen analysis was categorized as follows: 1/ never treated patients (n = 66); 2/ patients receiving NRTIs only (n = 49); 3/ patients receiving a NRTIs + protease inhibitor (PI) regimen (n = 144); 4/ patients receiving a NRTIs + non-nucleosidic reverse transcriptase inhibitor (NNRTI) regimen (n = 119). Semen parameters were assessed through standard semen analysis. Additional analyses included measurement of sperm motion parameters using computer-assisted semen analysis, seminal bacteriological analysis, seminal biochemical markers and testosterone plasmatic levels. All analyses were performed in the Cochin academic hospital. The data were analyzed through multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm motility was the only semen parameter which significantly varied according to treatment status. The median percentage of rapid spermatozoa was 5% in the group of patients receiving a regimen including efavirenz versus 20% in the other groups (P < 0.0001). Accordingly, sperm velocity was reduced by about 30% in this group (P < 0.0001). The role of chance was minimized by the strict definition and the size of the study population, which included a large enough group of never treated patients, the controlled conditions of semen collection and analysis, the multivariate analysis, the specificity and the high significance level of the observed differences. LIMITATIONS, REASONS FOR CAUTION: The design of the study did not allow demonstrating a causal link between exposure to efavirenz and sperm motility. WIDER IMPLICATIONS OF THE FINDINGS: As efavirenz is widely used in current antiretroviral therapy, these findings may concern many HIV-infected men wishing to have children. This justifies further assessment of the consequences on fertility of the exposure to efavirenz. Moreover, the possibility of common cellular impacts underlying adverse effects of efavirenz in sperm cells and neurons deserved investigation. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. None of the authors has any conflict of interest to declare.

[In vitro fertilization and systemic lupus erythematosus or antiphospholipid syndrome: An update]. / Fécondation in vitro au cours du lupus érythémateux systémique ou du syndrome des antiphospholipides : mise au point.

Fertility is not impaired in systemic lupus erythematosus or antiphospholipid syndrome, but, similarly to the general population, these patients may undergo in vitro fertilization. This type of treatment increases the risk of lupus flare, thrombosis, and ovarian hyperstimulation syndrome. This review will focus on in vitro fertilization in systemic lupus erythematosus or antiphospholipid syndrome. Literature data are relatively scant with only 3 reported studies. The first one included 17 patients and 63 cycles of induction ovulation/in vitro fertilization leading to 25 % of lupus flare, no thrombosis, and 3 % of ovarian hyperstimulation syndrome. The second study included 10 patients and 40 cycles of in vitro fertilization showing 31 % of lupus flare, no thrombosis and no ovarian hyperstimulation syndrome. The last one included 34 patients and 83 procedures of in vitro fertilization leading to 8 % of flares, 5 % of thrombosis and no ovarian hyperstimulation syndrome. Interestingly, in this last study, half of the complications were explained by poor adherence to treatment. These data are reassuring but it is important to remember that in vitro fertilization should be scheduled and carefully supervised in the same way as the high-risk pregnancies occurring in these patients.

[Pre-washing catheter dramatically improves the post intrauterine insemination pregnancy rate]. / Le rinçage des cathéters avant insémination intra-utérine augmente considérablement les taux de grossesses.

OBJECTIVE: To analyze the effectiveness of pre-washing the intrauterine insemination catheters on IUI outcome. PATIENTS AND METHODS: Infertile couples (n=322) involved in a IUI program were included in the study. IUI indications were cervical factors, ovulation dysfunction, cryopreserved semen and unexplained infertility. Every other week for two years, IUI catheters were washed with culture medium prior to intrauterine sperm insemination. RESULT(S): Only the first IUI for each couple were analyzed. Washing the catheter, prior to use, resulted in a 49.7% increase in clinical pregnancy rate (22.0% vs 14.7% P<0.05). This result is observed with fresh sperm (15.7% vs 11.1%) and frozen-thawed sperm as well (31.1% vs 19.8%). The early pregnancy termination rate was similar in all groups. DISCUSSION AND CONCLUSION: Pre-washing the catheter before IUI should be recommended in Good Laboratory Practice Guidelines as it is already the case for embryo transfer catheters. This raises the problem of washing all single-use devices, in contact with gametes or embryos during IVF.