Valérie Vernaeve

Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial

Aim. To compare donor and recipient outcome after inducing the final oocyte maturation with hCG or GnRH agonist in GnRH-antagonist treated oocyte donation (OD) cycles. Methods. Two-hundred fifty-seven oocyte donors were enrolled to participate in a clinical trial in a private fertility centre. After stimulation with 225 IU rFSH and Cetrorelix 0.25 mg/day, 212 oocyte donors were randomised with sealed envelopes for triggering with recombinant hCG (Ovitrelle 250 μgr, n = 106) or a GnRH agonist (triptorelin 0.2 mg, n = 106). Results. The number of retrieved COCs (12 ± 6.3 vs 11.4 ± 6.4), mature oocytes (8 ± 4.6 vs 7.5 ± 4.1), the proportion of mature oocytes (67.2 ± 20.4% vs 67.1 ± 20.9%) and fertilisation rates (67.8 ± 23.5% vs 71.1 ± 22.1%) were comparable. Clinical, ongoing pregnancy and live birth rates were not statistically different in the corresponding recipient groups. Nine cases of mild and one case of severe OHSS occurred in hCG group, whereas no cases were detected in GnRH agonist group. Conclusions. The findings of our RCT suggest that donor and recipient outcome are comparable in OD cycles triggered with hCG or a GnRH agonist. Furthermore, the risk of OHSS seems to be reduced considerably, therefore the combination of a GnRH antagonist protocol with GnRH agonist triggering constitutes a safe treatment option for egg-donors.

Decreased pregnancy rate after in-vitro fertilization in HIV-infected women receiving HAART.

A study on in-vitro fertilization (IVF) was conducted among HIV-infected women. In these patients, a reduced pregnancy rate after IVF was observed if the patients own oocytes were used. However, no significant reduction in the pregnancy rate was found if donated oocytes were used. The CD4 lymphocyte count was independently associated with ovarian resistance to hyperstimulation. Subclinical hypogonadism mediated by immunosuppression may explain these observations, suggesting the need to optimize the immunological status of the patient before considering assisted reproduction treatments.

Fertility assessment in non-infertile HIV-infected women and their partners

The objective of the study was to assess the fertility of non-infertile couples seeking pregnancy in whom the woman was HIV infected. Therefore, a cross-sectional study was conducted between January 1998 and March 2005. A standardized fertility assessment was performed in all the included couples. A total of 130 women and 121 men were evaluated. Their median age was 34 years (range 22-43). Only 7.2% of the women were severely immunocompromised. The majority of women had regular cycles. Only one woman had an active sexually transmitted disease at the time of evaluation. A tubal occlusion on hysterosalpingogram was present in 27.8% of the women with no proven fertility. In 50.5% of the women, hepatitis C virus co-infection was present. One-third of the male partners (38/121) was infected with HIV. Abnormal semen parameters were observed in 83.4% of HIV-infected and 41.7% of HIV-uninfected partners (OR = 7; 95% CI = 2.1-23). It is concluded that the great majority of the HIV-infected women seeking pregnancy had a good infection status. Because in many of the couples, the women presented unexplained tubal occlusions and the men presented semen alterations, a hysterosalpingography and semen analysis should be part of the preconceptional investigations.

Is oocyte donation a risk factor for preeclampsia? A systematic review and meta-analysis.

PurposeThe objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved by in vitro fertilization with autologous oocytes (IVF).MethodsA systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The 11 studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome).ResultsOocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (REM: heterogeneity between the studies). The meta-regression analysis showed that neither multiple pregnancies (estimate = 0.08; p = 0.19) nor patient age (estimate = −2.29; p = 0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (p = 0.237), suggesting absence of heterogeneity between the studies.ConclusionsPregnancies achieved by oocyte donation confer a threefold increase in the likelihood of developing PE than those achieved by in vitro fertilization with own oocytes. Physicians should be aware of this risk in order to both counsel patients and monitor pregnancies accordingly.

Transvaginal versus transabdominal ultrasound guidance for embryo transfer in donor oocyte recipients: a randomized clinical trial

OBJECTIVE To compare pregnancy and implantation rates with transvaginal (TV) versus transabdominal (TA) ultrasound-guided embryo transfer (ET). DESIGN Randomized, clinical trial registered at clinicaltrials.gov (NCT 01137461). SETTING Private, infertility clinic. PATIENT(S) Three-hundred thirty randomized recipients of donor oocytes. INTERVENTION(S) Embryo transfer using TV (with empty bladder, using the Kitazato ET Long catheter) versus TA ultrasound guidance (with full bladder, using the echogenic Sure View Wallace catheter). MAIN OUTCOME MEASURE(S) Overall pregnancy, clinical pregnancy, implantation, and ongoing pregnancy rates. Duration and difficulty of ET. Patient-reported uterine cramping and discomfort, as evaluated by questionnaire. RESULT(S) No statistically significant differences were observed in clinical pregnancy 50.9% versus 49.4% (95% confidence interval of the difference: -9.2 to +12.2%), implantation 34.5% versus 31.4% (95% CI of the difference: -4 to +10.3%) between the TV and TA ultrasound-guided groups. Transfer difficulty (6% versus 4.2%) and uterine cramping (27.2% versus 18.3%) were not statistically significantly different between treatment groups. Total duration (154±119 versus 85±76 seconds) was statistically significantly higher in the TV ultrasound group. Light to moderate-severe discomfort related to bladder distension was reported by 63% of the patients in the TA ultrasound group. CONCLUSION(S) Transvaginal ultrasound-guided ET yielded similar success rates compared with the TA ultrasound-guided procedure without requiring the assistance of a sonographer. It was associated with increased patient comfort due to the absence of bladder distension.

Empty follicle syndrome prevalence and management in oocyte donors

STUDY QUESTION Is the drug used for final oocyte maturation a factor in determining the prevalence of empty follicle syndrome (EFS)? SUMMARY ANSWER The drug used for final oocyte maturation is not a factor in determining the prevalence of EFS among women unaffected by infertility. WHAT IS KNOWN ALREADY Despite satisfactory follicular stimulation and adequate follicular development, cases of EFS, i.e. failure to recover any cumulus oocyte complex, have been reported both with hCG and GnRH agonist triggering. No standard management protocol has been proposed so far. STUDY DESIGN, SIZE, DURATION Retrospective analysis of oocyte donation cycles performed between August 2006 and April 2013 in a large private fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS The analysis included 12 483 oocyte donation cycles of which 74 were EFS cycles. All cycles were triggered with either hCG or GnRH agonists. MAIN RESULTS AND THE ROLE OF CHANCE There were no differences in the gonadotropic stimulation, pituitary suppression and triggering drug between cycles where oocytes were recovered successfully and EFS cycles. The total prevalence of EFS was 0.59%. Given the rarity of the syndrome, caution is advised when interpreting the analysis. LIMITATIONS, REASONS FOR CAUTION The main limitation of this study is its retrospective nature. Although this is the largest analysis of EFS in donors reported so far, its statistical power is limited because the syndrome has a low incidence. In some cycles of EFS from 2006 to 2007 there is a lack of hormone data. WIDER IMPLICATIONS OF THE FINDINGS Our findings may be generalized to oocyte donors and IVF patients younger than 35 years old, with cycles undergoing final maturation triggering with either hCG or GnRH agonists. The generalization cannot be extended to patients with an ovarian factor as the cause of their reproductive pathology. The theoretical aetiology of a temporary hypothalamic-pituitary hyposensitivity can explain the cycles where a rescue protocol with hCG has been successful. STUDY FUNDING/COMPETING INTERESTS This work was supported in part by funding from Fundaciò EUGIN. The authors have no conflicts to declare. TRIAL REGISTRATION NUMBER NA.

Increasing fertility knowledge and awareness by tailored education: a randomized controlled trial

Women of reproductive age have insufficient fertility knowledge and awareness. Reproductive lifespan and assisted reproduction are the primary areas in which awareness is lacking. Relatively simple interventions can be used to increase knowledge among university students; however, no intervention has been tested to date in a population with more varied education levels. The aim of this study was to evaluate which intervention most improved fertility knowledge in women attending a fertility centre for oocyte donation. A randomized controlled trial was conducted with three intervention groups: tailored, untailored and control. A questionnaire was administered on the day of the first consultation, and again at the oocyte retrieval. Two hundred and one women were enrolled and completed the pre-test, 109 started the cycle and 90 completed the post-test. The effect of the intervention was measured as the difference between the groups in their score from the pre-test to the post test. Only the tailored group showed a significant increase (+2.5; 95% CI [1.8, 3.3]; P = 0.001). Information relating to a womans most fertile age and limits for childbearing were the most useful. Tailored oral education, therefore, increases fertility knowledge in young women, particularly in relation to their fertility lifespan.

Learning Curves in 3-Dimensional Sonographic Follicle Monitoring During Controlled Ovarian Stimulation

Three‐dimensional (3D) sonographically based automated volume calculation (SonoAVC; GE Healthcare, Zipf, Austria) is being introduced in folliculometry during ovarian stimulation; however, clear training assessments in this technique are lacking. The learning curve–cumulative summation (LC‐CUSUM) test provides a quantitative tool to determine when a trainee has learned a procedure. The aim of this prospective study was to assess 3D SonoAVC LC‐CUSUM curves in folliculometry.

Menstrual cycle length in reproductive age women is an indicator of oocyte quality and a candidate marker of ovarian reserve

OBJECTIVE The menstrual cycle is a finely tuned biological process comprising a precisely orchestrated sequence of events: follicular growth, selection and ovulation, extensive endometrial changes, corpus luteum (CL) growth and maturation, and luteolysis. Differences in the length of the menstrual cycle (MCL) have been associated with variable female fecundity. However, the reason for these differences is so far unknown. The donor-recipient model, separating uterine from ovarian factors, allows clarifying the origin of MCL-associated fecundity variations. STUDY DESIGN We analyzed retrospectively 2015 oocyte donation cycles, resulting in 3427 embryo transfers (ET) and pregnancy follow-up. RESULTS Surprisingly, we found that oocyte donors MCL of 34-35 days were strongly associated with significantly higher biochemical, clinical and ongoing pregnancy rates in woman who received the embryos, compared to the reference group of MCL of 27-29 days. Moreover, donors with longer MCL presented higher ovarian response to stimulation and lower amount of hormonal stimulation needed to achieve multifollicular growth. Conversely, MCL of <25 days were associated with a poorer ovarian response to stimulation, less cumulus oocyte complexes (COCs) and less mature oocytes (MII) retrieved; however, the quality of oocytes in these women is not associated to their ovarian response, as evidenced by the pregnancy rates obtained when transferred into an adequately prepared endometrium. CONCLUSIONS We conclude that oocyte quality, rather than natural endometrial preparation, is the main reason for the reported higher fecundity of women with longer MCL. This result is further confirmed by our data on bleeding length in the donor pool. Response to ovarian stimulation is the definitive test of ovarian reserve; moreover, since different MCLs result from varying length of the follicular phase, longer MCL should be associated with a higher number of follicular recruitment events. We hypothesize that MCL is associated with - and a marker of - ovarian reserve in healthy reproductive age women.

Racial disparity in oocyte donation outcome: a multiethnic, matched cohort study

BACKGROUND Race and ethnicity are one of the newly investigated patient-related prognostic factors that might affect the outcome of assisted reproduction techniques. To our knowledge no data currently are available on the effect of race on oocyte donation outcome. MATERIALS A retrospective, matched cohort study was performed in a private infertility centre evaluating 1012 Black, South-East Asian and Caucasian recipients undergoing their first oocyte donation cycles. RESULTS A significantly lower ongoing pregnancy rate (24.6 versus 36.8%, OR: 0.56 95% CI: 0.40-0.77, P = 0.01) was observed among Black recipients compared with their matched Caucasian counterparts. The prevalence of uterine fibroids (49.6 versus 17.1%, P < 0.0001) and previous history of tubal infertility (53.2 versus 16.5%, P < 0.0001) was significantly higher among Black women. Multiple logistic regression analysis showed that, after adjusting for confounding variables, Black race was an independent risk factor for not achieving an ongoing pregnancy (for ongoing pregnancy, adjusted OR: 0.62 95% CI: 0.43-0.89, P = 0.009). Ongoing pregnancy rate (37.2 versus 37.2%, OR: 1.0 95% CI: 0.49-2.04, P = 1.0) was not significantly different between South-East Asian and matched Caucasian patients. CONCLUSIONS Black race was an independent risk factor for not achieving an ongoing pregnancy after oocyte donation. Although yellow race does not seem to adversely affect oocyte donation, larger studies are still warranted to draw more solid conclusions. Race should be considered as an independent prognostic factor in oocyte donation.