Melvin H. Thornton

Understanding the motivations, concerns, and desires of human immunodeficiency virus 1-serodiscordant couples wishing to have children through assisted reproduction.

OBJECTIVE To survey the attitudes of human immunodeficiency virus (HIV)–serodiscordant couples interested in assisted reproduction and better characterize their motivations for reproducing. METHODS A prospectively designed questionnaire and open-ended interview of 50 consecutive HIV-serodiscordant couples interested in undergoing assisted reproduction to avoid transmission of virus were studied. Demographic characteristics and attitudes regarding beginning a family were obtained. By design, males were HIV seropositive (age, 38.0 ± 5.4 years, range 26–51 years) and healthy. Women were HIV seronegative (age, 34.5 ± 5.1 years, range 24–45 years). Most couples were married (44 of 50) and in long-term relationships (duration of relationship, 8.9 ± 4.9 years, range 1–20 years). RESULTS Before presentation, nine of 50 couples had conceived and delivered a child (three of nine instances with knowledge of paternal HIV status). Previous timed intercourse occurred in 8% of couples (four of 50). Six individuals stated they would proceed with timed intercourse if no other alternatives existed. Forty-eight percent said they would prefer artificial insemination with donor sperm in lieu, if assisted reproduction failed or were unavailable. Forty-three percent of respondents would pursue “posthumous conception” if cryopreserved sperm or embryos were available in the event of the partners death. Most couples discussed the possibility of single parenting (45 of 50; 90%) or the possibility for adoptive parenting (29 of 50; 58%). Couples were aware of risk, and 92% (46 of 50) understood that their child might contract HIV. CONCLUSION Human immunodeficiency virus–serodiscordant couples are actively seeking reproductive assistance and often consider or practice unsafe measures to achieve pregnancy. Reproductive issues and concerns unique to these couples need to be addressed before treatment.

Assessing the clinical utility of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus type 1 serodiscordant couples: report of 113 consecutive cycles

OBJECTIVE To assess the utility and safety of in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) in human immunodeficiency virus-1 (HIV-1) serodiscordant couples. DESIGN Retrospective study. SETTING University-based practice. PATIENT(S) HIV-1 seropositive men and seronegative women undergoing IVF-ICSI.IVF-ICSI, HIV testing of female partner and infants. MAIN OUTCOME MEASURE(S) IVF performance, pregnancy rates, and HIV-1 seroconversion rate. RESULT(S) We initiated 113 IVF cycles in 61 serodiscordant couples. Due to poor ovarian response, 11.5% of cycles were canceled. The number of oocytes collected per retrieval was 17.11 +/- 9.52 (2 to 47), yielding 13.90 +/- 8.12 (1 to 42) mature oocytes suitable for ICSI, and 9.34 +/- 5.45 (0 to 24) normal fertilized oocytes. We transferred 3.54 +/- 1.09 (1 to 6) embryos. The overall clinical pregnancy rate was 44.8% per embryo transfer (ET); ongoing/delivered pregnancy rate was 36.5% per ET, with a 57.1% multiple gestation rate. Cumulatively, 50.8% of couples achieved a successful pregnancy through IVF-ICSI, 54.1% when including frozen ET cycles. There were no HIV-1 seroconversions in patients or delivered babies. CONCLUSION(S) HIV-1 serodiscordant couples who undergo IVF-ICSI to avoid disease transmission experience high rates of success, but also encounter complications from assisted reproductive technology similar to traditional patients. The best candidates appear to be younger women without strong risk factors for ovarian hyperstimulation syndrome.

Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.

The association between anti-Müllerian hormone and IVF pregnancy outcomes is influenced by age.

The conflicting results from studies on the predictive capabilities of serum anti-Müllerian hormone (AMH) for IVF pregnancy outcomes may be attributed to small sample sizes and disparities in the age of the study populations. The relationship between AMH and IVF pregnancy outcomes was clarified with retrospective cross-tabulation analyses (n=1558) stratified by age to control for its confounding effects. Serum AMH concentrations were divided into tertiles (≤ 0.29, 0.30-1.20, ≥ 1.21 ng/ml) and ages into four groups (<34, 34-37, 38-41, ≥ 42 years). For women <34, having serum AMH in the lowest tertile did not reduce the chance of IVF pregnancy/live birth compared with those with higher AMH concentrations. For women 34-41, a significant positive relationship existed between serum AMH and pregnancy rates. For women ≥ 42, serum AMH concentrations ≤ 0.29 ng/ml were associated with a 3% chance of pregnancy, and women with AMH ≥ 1.21 ng/ml had the same pregnancy rate as women with concentrations 0.30-1.20 ng/ml. In conclusion, AMH has limited predictive value for IVF outcomes in the two extremes of female reproductive age; however, for women between 34 and 41, higher serum AMH concentrations are associated with significantly greater chances of pregnancy (P<0.01).

Successive pregnancies with delivery of two healthy infants in a couple who was discordant for human immunodeficiency virus infection

OBJECTIVE To describe two successive pregnancies resulting in two healthy infants in an HIV-discordant couple who underwent IVF-ICSI. DESIGN Case report. SETTING University-based infertility clinic. PATIENT(S) A couple seeking fertility treatment in which the male partner was seropositive for HIV-1. INTERVENTION(S) Controlled ovarian hyperstimulation and IVF-ET with ICSI. MAIN OUTCOME MEASURE(S) Pregnancy outcome and HIV-1 seroconversion. RESULT(S) The couple delivered two healthy infants on successive pregnancies with use of IVF-ET with ICSI. CONCLUSION(S) For HIV-discordant couples in which the male partner is seropositive for HIV-1, IVF with ICSI is a viable option.

Assessing the treatment efficacy of IVF with intracytoplasmic sperm injection in human immunodeficiency virus-1 (HIV-1) serodiscordant couples

The purpose of this study was to evaluate the treatment efficacy of using IVF-intracytoplasmic sperm injection (ICSI) in HIV serodiscordant couples interested in having children while minimizing the risk of viral transmission. This study reviews the cases of HIV serodiscordant couples (n = 142) seeking fertility treatment at an assisted reproductive centre. The main outcome measures were successful pregnancy rate and HIV seroconversion rate. In calculating crude pregnancy rates, only patients who were actually treated were taken into account. To compensate for cancelled patients, and patient drop-out, lifetable analysis was performed. Life-table analysis demonstrated that 37.0 +/- 5.0% of couples attain a successful pregnancy after one completed IVF-ICSI with embryo transfer (IVF-embryo transfer) cycle. Following two and three IVF-embryo transfer cycles, the pregnancy rates rose to 56.8 +/- 6.0 and 73.4 +/- 6.9% respectively. Overall pregnancy rates were inversely related to age. There were no HIV seroconversions in treated patients or in delivered babies. It is concluded that the use of IVF-ICSI to avoid disease transmission in HIV-1 serodiscordant couples desiring children appears to be safe and yields high rates of pregnancy. However, success is influenced by the womans age.

Providing assisted reproductive care to male haemophiliacs infected with human immunodeficiency virus: preliminary experience

Summary.  Outlined is our experience with couples in whom the male was both human immunodeficiency virus (HIV) seropositive and a haemophiliac who underwent assisted reproductive technologies (ART) in order to attain family goals while minimizing the risk of HIV transmission. We report their demographics, attitudes towards assisted reproduction, and ART performance and outcomes. The study included HIV serodiscordant couples (n = 11) who underwent ART at a university‐based infertility practice from August 1997 to May 2002. Prior to treatment, couples prospectively completed a survey regarding their demographics and attitudes towards assisted reproduction. All couples underwent ART and pregnancy outcomes were analysed. The majority of the patients were fully employed, college‐educated, in good health, married and motivated to have a child while minimizing the risk of HIV transmission. Eleven couples underwent 25 cycles of ART [19 in vitro fertilization (IVF) cycles; five frozen embryo transfer cycles; and one oocyte donation cycle] resulting in nine successful pregnancies. The ongoing/delivered pregnancy rate per initiated IVF cycle was 42.1% per embryo transfer. Eight of 11 (72.7%) couples achieved a successful pregnancy. More than half (six of 11; 54.5%) the couples conceived during their initial attempt. Four of nine (44.4%) pregnancies were multiple gestations, including three sets of triplets. All female recipients tested seronegative for HIV at 3 and 6 months post‐embryo transfer. All delivered babies (n = 8) tested seronegative for HIV at birth and 3 months postpartum. Four pregnancies are currently ongoing. ART should be considered for HIV serodiscordant couples with haemophilia who desire to have children in order to minimize the risk of viral infection.

Complications of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus serodiscordant couples

IntroductionOur experience with complications related to in vitro fertilization (IVF), particularly ovarian hyperstimulation syndrome (OHSS) and higher-order multiple gestations, in human immunodeficiency virus (HIV) serodiscordant couples undergoing IVF with intracytoplasmic sperm injection (ICSI) is presented.MethodsWe retrospectively evaluated 132 consecutive IVF-ICSI cycles and the ensuing 43 pregnancies in 74 HIV-seropositive male discordant couples. The diagnosis of moderate and severe OHSS was based on clinical criteria. Higher-order multiple gestations were defined as viable triplets or greater by the end of the first trimester verified by ultrasonography.ResultsThe incidence of moderate and severe OHSS was 4.5% of initiated IVF cycles. Seven of the 43 (16.3%) pregnancies were higher-order multiple gestations (1 quadruplet and 6 triplet pregnancies), resulting in the delivery of 3 sets of triplets and 3 sets of twins, with an ongoing twin pregnancy. Four patients had undergone multifetal pregnancy reduction to twins. There were no seroconversions in the women and the infants.ConclusionHIV serodiscordant couples undergoing fertility treatment with IVF-ICSI should be made particularly aware of the risks of higher-order multiple gestations and OHSS.

Serum Estradiol Levels after 4 Days of Ovarian Hyperstimulation in Oocyte Donors Are Predictive of Embryo Quality and Clinical Outcomes

Objective: To determine whether estradiol (E2) levels after 4 days of ovarian hyperstimulation in leuprolide-downregulated cycles are predictive of embryo quality and pregnancy outcome in oocyte donation. Material and Methods: Retrospective analysis of 287 consecutive oocyte donation cycles performed at a university assisted reproduction therapy program between January 1996 and December 2000. Oocyte donors and recipients followed a non-varied standard synchronization regimen. A serum E2 (day-5 E2) was obtained from egg donors the morning after leuprolide acetate downregulation and 4 days after hMG/FSH administration. Day-5 E2 was categorized into 3 groups: group I <75 pg/ml; group II 75–350 pg/ml, and group III ≧350 pg/ml. All embryo transfers were performed 3 days after oocyte recovery. Results: Elevated day-5 E2 levels were directly correlated with higher average embryo scores, greater number of oocytes retrieved, and greater number of embryos available for transfer and cryopreservation. Improved pregnancy outcomes were also noted for group III (day-5 E2 level >350 pg/ml). Conclusion: After 4 days of gonadotropin stimulation, an E2 level of >350 pg/ml is most predictive of higher embryo grade and pregnancy outcome in oocyte donation.