G. Kovalevsky

A randomized six-day safety study of an antiretroviral microbicide candidate UC781, a non-nucleoside reverse transcriptase inhibitor.

Goal: This study evaluated the effect of a single dose and 5 additional consecutive daily doses of UC781 gel at concentrations of 0.1%, 0.25%, 1.0%, and 0% on urogenital irritation. Study Design: Forty-eight healthy sexually abstinent women were randomly assigned to 1 of 4 groups. Methods: Urogenital irritation was assessed by pelvic examination, colposcopy, and reports of genital symptoms at baseline and after 1 and 6 doses. Vaginal health was assessed by wet mount and systemic safety by laboratory evaluation after 1 and 6 doses, and UC781 levels were assessed at baseline and after 6 doses. Results: Some evidence of urogenital irritation was common in all treatment groups and was most often transient and mild. Colposcopic findings were infrequent in the placebo group (8%) and more common in the 3 treatment groups (24%–42%). Edema, which may indicate underlying inflammation, was observed in the vaginal fornix of 2 women exposed to UC781. There was no apparent increase in vaginal infection or clinically significant changes in laboratory values. Two of 12 participants randomized to 1% UC781 gel had detectable plasma levels that were less than the lower level of quantification. Conclusions: UC781 was well tolerated in this initial dose ranging safety study when used once daily for 6 days in sexually abstinent women. Five safety/pharmacokinetic studies of UC781 are currently underway in women and men, all utilizing UC781 concentrations less than 1%, with twice-daily dosing in some studies, and all involving careful monitoring of exposed epithelium.

Do assisted reproductive technologies cause adverse fetal outcomes

Treatment for infertility using assisted reproductive technologies (ART) is highly successful and has been used to help a steadily growing number of couples worldwide. In 1999, in the United States, more than 86,000 treatment cycles were performed resulting in the birth of more than 30,000 babies. Despite this widespread application, few follow-up studies of children conceived through ART have been performed, and more rigorous investigation of this important issue has clearly been needed. In recent months, three studies linking ART with several complications have been published in high profile and widely read general medical journals: Schieve et al. (1) reported that singletons conceived using ART were at an increased risk for low birth weight, whereas Hansen et al. (2) suggested an increased risk of major birth defects. Finally, Stromberg et al. (3) concluded that children conceived through IVF have an increased risk of neurological problems, especially cerebral palsy.

Should embryos developing to blastocysts on day 7 be cryopreserved and transferred: an analysis of pregnancy and implantation rates

OBJECTIVE To compare pregnancy rates (PRs) using blastocysts cryopreserved on day 7 with those cryopreserved on days 5 and 6. DESIGN Retrospective observational cohort study. SETTING Infertility center performing IVF. PATIENT(S) Eight hundred women with infertility undergoing frozen ET. INTERVENTION(S) Blastocysts cryopreserved on days 5, 6, and 7 after retrieval were thawed and transferred. MAIN OUTCOME MEASURE(S) Ongoing PRs (pregnancy developing appropriately into the second trimester). Thaw survival, implantation rates, and clinical PRs were also calculated. RESULT(S) A total of 1,406 embryos were thawed with a survival of 90.7% for day 5, 83.7% for day 6, and 78.7% for day 7. Implantation rates were 43.3%, 28.9%, and 28.9%, respectively. Ongoing PRs were 43.9%, 32.9%, and 26.7%, respectively. CONCLUSION(S) Blastocysts cryopreserved on day 7 have a lower, but clinically important potential. Embryos that do not achieve blastocyst stage on day 6 should not be universally discarded, but should be observed in culture 1 more day as 27% may result in an ongoing pregnancy.

Norplant and other implantable contraceptives.

Implantable contraception represents a safe, reversible form of long-term family planning with distinct advantages. It does not contain estrogen, thus avoiding many of it contraindications. Importantly, it is extremely effective, has high continuation rates, and is well tolerated. The main side effects of Norplant are irregular menstrual bleeding and the occasional difficult removal. Although recent high-profile litigation has severely diminished enthusiasm for Norplant, the FDA has reaffirmed its safety and efficacy. Norplant remains a viable family planning option for carefully selected women. New contraceptive implants may soon be available accentuating the advantages of Norplant while minimizing the disadvantages.

Levonorgestrel effects on serum androgens, sex hormone–binding globulin levels, hair shaft diameter, and sexual function

OBJECTIVE To determine the effects of levonorgestrel (LNG) on serum androgens, sex hormone-binding globulin (SHBG), hair shaft diameter, and sexual function in women. DESIGN Substudy of a prospective randomized double-blind study in women using an LNG SC implant (LNG-SI), who were treated with doxycycline or placebo. SETTING Medical school department of obstetrics and gynecology. PATIENT(S) Forty women were enrolled; 36 completed the study. INTERVENTION(S) Participants were randomized to doxycycline 20 mg or an identical placebo orally twice a day after LNG-SI insertion. MAIN OUTCOME MEASURE(S) Serum levels of total T (TT), free T (FT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), androstanediol glucuronide (AG), SHBG, and LNG; hair shaft diameter; and sexual function using the Brief Index of Sexual Function for Women and the Arizona Sexual Experiences Scale were assessed. RESULT(S) Serum TT, A, DHT, DHEAS, and SHBG declined after LNG-SI insertion. No changes were found in FT, AG, hair shaft diameter, or sexual function. Serum LNG correlated with SHBG levels. There were no differences between the placebo and doxycycline groups. CONCLUSION(S) LNG reduced serum TT, A, DHT, DHEAS, and SHBG but had no effect on sexual function or markers of androgen bioactivity.