Juliette Guibert

Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network.

Objective:To examine the safety and effectiveness of assisted reproduction using sperm washing for HIV-1-serodiscordant couples wishing to procreate where the male partner is infected. Design and methods:A retrospective multicentre study at eight centres adhering on the European network CREAThE and involving 1036 serodiscordant couples wishing to procreate. Sperm washing was used to obtain motile spermatozoa for 3390 assisted reproduction cycles (2840 intrauterine inseminations, 107 in-vitro fertilizations, 394 intra-cytoplasmic sperm injections and 49 frozen embryo transfers). An HIV test was performed in female partners at least 6 months after assisted reproduction attempt. The outcome measures recorded were number of assisted reproduction cycles, pregnancy outcome and HIV test on women post-treatment. Results:A total of 580 pregnancies were obtained from 3315 cycles. Pregnancy outcome was unknown in 47 cases. The 533 pregnancies resulted in 410 deliveries and 463 live births. The result of female HIV testing after assisted reproduction was known in 967 out of 1036 woman (7.1% lost to follow-up). All tests recorded were negative. The calculated probability of contamination was equal to zero (95% confidence interval, 0–0.09%). Conclusion:This first multicentre retrospective study of assisted reproduction following sperm washing demonstrates the method to be effective and to significantly reduce HIV-1 transmission risk to the uninfected female partner. These results support the view that assisted reproduction with sperm washing could not be denied to serodiscordant couples in developed countries and, where possible, could perhaps be integrated into a global public health initiative against HIV in developing countries.

Assisted reproduction in Hiv-1-serodifferent couples: the need for viral validation of processed semen

Background: Many HIV-infected men and women have a strong desire for a child. Assisted reproductive technologies (ART) are an option for HIV-serodifferent couples to reduce the risk of HIV transmission from an infected man to the woman. Potential HIV contamination of selected spermatozoa after semen processing is an important issue in this context. Methods: HIV in processed semen obtained in our laboratory since 1995 were analysed. HIV RNA and DNA detection was performed in the selected spermatozoa of 125 men. HIV RNA was analysed in blood and semen plasma as well as HIV DNA in non-sperm cells. Results: HIV RNA and DNA were detected in the selected spermatozoa of eight and two men (6.4% and 1.6%), respectively. HIV RNA was detected with a median load of 5 copies/106 spermatozoa. Six of the eight men were untreated, one was taking nucleoside analogue therapy and one was on highly active antiretroviral treatment (HAART). HIV RNA detection was more likely to be positive in selected spermatozoa of men with high seminal plasma viral load. HIV RNA was detected in 26% and 11% of selected spermatozoa fractions when the seminal plasma load was > 10 000 copies/ml and 20–10 000 copies/ml, respectively, but in none when the seminal plasma tested negative. Conclusion: Selected spermatozoa may be positive for HIV RNA detection even in treated patients. Viral validation of processed semen is necessary in ART programmes for serodifferent couples, particularly in men with only partially or poorly controlled HIV infection.

Long-term outcome of parenthood project during in vitro fertilization and after discontinuation of unsuccessful in vitro fertilization.

OBJECTIVE To explore the long-term outcome of patients who began IVF treatment by considering not only treatment outcome in the center but also the parenthood project outcome after discontinuation of unsuccessful IVF. DESIGN Retrospective cohort follow-up study. SETTING Two French IVF centers. PATIENT(S) Seven hundred twenty-four patients who began IVF treatment in 1998. INTERVENTION(S) Postal and phone contacts with unsuccessful IVF patients. MAIN OUTCOME MEASURE(S) Long-term outcome of parenthood project. RESULT(S) Of the 724 patients, a minimum of 53% and a maximum of 81% finally succeeded in their parenthood project during or after IVF treatment (depending on the hypotheses that the 204 patients not contacted either failed or succeeded in their parenthood project). An intermediate hypothesis gave an estimation of 66% of patients finally succeeding in having a child (40% during IVF treatment in the center and 26% after). Achievement of the parenthood project after IVF discontinuation was due mainly to adoption of a child (46%) or a birth following a spontaneous pregnancy (42%). CONCLUSION(S) Unsuccessful patients should not lose hope, because nearly half may subsequently succeed in having a child.

Spontaneous pregnancies among couples previously treated by in vitro fertilization

OBJECTIVE To determine the frequency of live births following spontaneous pregnancy (BSP) and to examine their associated factors among couples who have unsuccessfully or successfully experienced fertility treatments. DESIGN Retrospective cohort. SETTING Eight IVF centers. PATIENT(S) A total of 2,134 couples who began IVF treatment in the centers in 2000-2002 and were followed up by a postal questionnaire sent 7-9 years after they started treatment in the inclusion center. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Rates of BSP and factors associated with BSP. Univariate and multivariate analyses were conducted using logistic regression. RESULT(S) The BSP rate was 17% (218/1,320) among couples who had previously had a child through medical treatment and 24% (193/814) among couples who had remained childless after treatment. In both groups, the probability of BSP was higher among younger women and increased with a smaller number of IVF attempts. Probability was also higher when the cause of infertility was unexplained. CONCLUSION(S) Our results should give hope to couples who have been unsuccessfully treated by IVF, especially young couples with unexplained infertility. Nonetheless, it should be remembered that the BSP rates are cumulative rates observed over a long period of time and that these couples have a very low monthly probability of conceiving.

Low dose recombinant FSH treatment may reduce multiple gestations caused by controlled ovarian hyperstimulation and intrauterine insemination

Objective  To evaluate the rate of multiple pregnancies in intrauterine insemination cycles stimulated with a minimal dose of recombinant follicle stimulating hormone (rec‐FSH).

Effect of the woman’s age on discontinuation of IVF treatment

Treatment discontinuations are an important issue in IVF programmes. In the French context, financial constraint does not intervene in discontinuation until older ages. This study examined treatment discontinuation in IVF programmes, according to the womans age and when there is no financial burden for couples. Medical records were collected for 3037 women who began their IVF programme between 1998 and 2002 in two French IVF units. Up to four attempts were taken into consideration. Cumulative success (delivery) rates were calculated, as well as discontinuation rates. Multiple imputation was applied to estimate a theoretical cumulative success rate as if no woman discontinued treatment before the end of the IVF programme without delivering. Cumulative discontinuation rates at the end of the IVF programme increased with the womans age (41% for age <35, 56% for age 35-39, 80% for age ⩾40). The benefit in terms of delivery rates of pursuing treatment would be smaller for older women (∼10% for age <35, 7% for age 35-39, 4% for age ⩾40). Even when treatment is reimbursed, the discontinuation rate is high for older women, suggesting that the strong decrease in success rate with age induces older women to discontinue. Treatment discontinuations are an important issue in IVF programmes. In the French context, financial constraint does not intervene in discontinuation until older ages. We aimed to examine treatment discontinuation in IVF programmes, according to the womans age and when there is no financial burden for couples. Medical records were collected for 3037 women who began their IVF programme between 1998 and 2002 in two French IVF units. Up to four attempts were taken into consideration. Cumulative success (delivery) rates were calculated, as well as discontinuation rates. Multiple imputation was applied to estimate a theoretical cumulative success rate as if no woman discontinued treatment before the end of the IVF programme without delivering. Cumulative discontinuation rates at the end of the IVF programme increased with the womans age (41% for age <35, 56% for age 35-39, 80% for age ⩾40). The benefit in terms of delivery rates of pursuing treatment would be smaller for older women (∼10% for age <35, 7% for age 35-39, 4% for age ⩾40). Even when treatment is reimbursed, the discontinuation rate is high for older women, suggesting that the strong decrease in success rate with age induces older women to discontinue.

Optimal timing for oocyte denudation and intracytoplasmic sperm injection.

Objectives. To analyze the impact of oocyte denudation and microinjection timings on intracytoplasmic sperm injection (ICSI) outcomes. Study Design. We included ICSI cycles with the following parameters: rank 1 or 2, female age <36 years, male factor infertility, long protocol using GnRH agonist and rFSH for ovarian stimulation, and use of freshly ejaculated sperm (n = 110). Several ICSI parameters were analyzed according to the time between oocyte retrieval and denudation (T 1) and the time between denudation and ICSI (T 2) using a statistical logistic regression analysis. Results. Neither T 1 nor T 2 had a significant influence on the Metaphase II (MII) rate but the fertilisation rate (FR) showed a significant improvement when T 1 was longer (optimal results at T 1 = 3 hours) while FR significantly decreased with the increase of T 2. Optimal implantation (IR) and pregnancy (PR) rates were obtained when T 1 was around 2 hours. Conclusion. Incubation of oocytes around 2 hours between retrieval and denudation may not increase MII rate but appears to lead to the optimal combination of FR and IR.

Who does not participate in a follow-up postal study? a survey of infertile couples treated by in vitro fertilization

BackgroundA good response rate has been considered as a proof of a study’s quality. Decreasing participation and its potential impact on the internal validity of the study are of growing interest. Our objective was to assess factors associated with contact and response to a postal survey in a epidemiological study of the long-term outcome of IVF couples.MethodsThe DAIFI study is a retrospective cohort including 6,507 couples who began an IVF program in 2000-2002 in one of the eight participating French IVF centers. Medical data on all 6,507 couples were obtained from IVF center databases, and information on long-term outcome was available only for participants in the postal survey (n = 2,321). Logistic regressions were used to assess firstly factors associated with contact and secondly factors associated with response to the postal questionnaire among contacted couples.ResultsSixty-two percent of the 6,507 couples were contacted and 58% of these responded to the postal questionnaire. Contacted couples were more likely to have had a child during IVF treatment than non-contactable couples, and the same was true of respondents compared with non-respondents. Demographic and medical characteristics were both associated with probability of contact and probability of response. After adjustment, having a live birth during IVF treatment remained associated with both probabilities, and more strongly with probability of response. Having a child during IVF treatment was a major factor impacting on participation rate.ConclusionsNon-response as well as non-contact were linked to the outcome of interest, i.e. long-term parenthood success of infertile couples. Our study illustrates that an a priori hypothesis may be too simplistic and may underestimate potential bias. In the context of growing use of analytical methods that take attrition into account (such as multiple imputation), we need to better understand the mechanisms that underlie attrition in order to choose the most appropriate method.

Joint modeling of success and treatment discontinuation in in vitro fertilization programs: a retrospective cohort study.

BackgroundAs discontinuation in in vitro fertilization (IVF) programs has been associated with a poor prognosis, one hypothesis is that some couple-specific predictive factors in IVF may be shared with opposite effect by both success (i.e. live birth) and treatment discontinuation processes. Our objective was to perform a joint analysis of these two processes to examine the hypothesis of a link between the two processes.MethodsAnalyses were conducted on a retrospective cohort of 3,002 women who began IVF between 1998 and 2002 in two French IVF centers: a Parisian center and a center in a medium-sized city in central France. A shared random effects model based on a joint modelization of IVF treatment success and discontinuation was used to study the link between the two processes.ResultsSuccess and discontinuation processes were significantly linked in the medium-sized city center, whereas they were not linked in the Parisian center. The center influenced risk of treatment discontinuation but not chance of success. The well-known inverse-J relation between the woman’s age and chance of success was observed, as expected. Risk of discontinuation globally increased as the woman’s age increased.ConclusionsThe link between success and discontinuation processes could depend on the fertility center. In particular, the woman’s decision to pursue or to discontinue IVF in a particular center could depend on the presence of other IVF centers in the surrounding area.

Seven out of 10 couples treated by IVF achieve parenthood following either treatment, natural conception or adoption

The aim of this study was to explore the achievement of parenthood 8 years after starting IVF, considering multiple pathways to parenthood during and after IVF treatment. Medical data on 6507 couples who began IVF between 2000 and 2002 were obtained from the databases of eight French IVF centres. Information on long-term outcome was available for participants in the 2008-2010 postal survey. Multiple imputation methods were used to account for missing data. Eight years after starting IVF, 71% (95% CI 69 to 74) of treated couples had a child. This included 41% live births after IVF in the IVF centre, 7% live births after another treatment or after IVF in another centre, 12% live births after spontaneous conception and 11% adoptions. This study provides a longitudinal overview of paths to parenthood among couples successfully and unsuccessfully treated by IVF. These results should give hope to infertile couples as seven out of 10 couples finally became parents. However, IVF is not the only path to parenthood, and couples should be informed of the other possible avenues.