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.

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.

Ovarian activity and safety of a novel levonorgestrel/ethinyl estradiol continuous oral contraceptive regimen.

BACKGROUND: A continuous regimen of oral levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg was evaluated for inhibition of ovulation, time to return to ovulation after stopping treatment and safety. STUDY DESIGN: This open-label study was conducted in healthy women aged 18-35 years. Ovulation was documented before treatment, and then participants received oral tablets containing LNG 90 mcg/EE 20 mcg to be taken continuously for three 28-day intervals. Ovarian activity was assessed three times per week during the treatment period with transvaginal ultrasound scans and measurements of serum 17beta-estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone concentrations. Safety assessments included physical examinations, laboratory evaluations and adverse event records. RESULTS: Thirty-seven of the 58 subjects who received treatment met predefined criteria for efficacy analysis. No on-treatment ovulations occurred in the efficacy or intent-to-treat population. There was evidence of ovulation within 37 days of stopping treatment for 46 (98%) of 47 subjects evaluated posttreatment. The final subject with a history of polycystic ovarian syndrome ovulated by Day 66. The safety profile observed during this 84-day continuous regimen was similar to that seen with other low-dose oral contraceptives administered in a cyclic regimen. CONCLUSIONS: The continuous LNG/EE regimen completely inhibited ovulation, with little evidence of follicular development and with rapid return of ovulatory capacity after stopping treatment.

Is factor V Leiden mutation a cause of in vitro fertilization failure?

This prospective cohort study tested whether the most common hereditary thrombophilia, factor V Leiden (FVL) mutation, is associated with nonpregnancy after IVF. Factor V Leiden mutation prevalence was very low (1.6%) and had a preliminarily positive association with pregnancy, suggesting that routine testing in a general IVF population for FVL mutation as a cause of IVF failure and infertility is not indicated.

Effects of doxycycline on serum and endometrial levels of MMP-2, MMP-9 and TIMP-1 in women using a levonorgestrel-releasing subcutaneous implant.

BACKGROUND: Endometrial spotting and/or bleeding (ESB) occurs in levonorgestrel subcutaneous implant (LNG SI) users. Matrix metalloproteinases (MMPs) may play a role in ESB. STUDY DESIGN: Women between 18 and 40 years with regular menstrual cycles had a baseline evaluation followed by LNG SI insertion and randomization to doxycycline (DOX; 20 mg) or placebo (PL) twice a day. MMP-2, MMP-9 and tissue inhibitor of MMP-1 (TIMP-1) in serum and the endometrium were estimated at baseline and at 1, 3 and 6 months after insertion. RESULTS: LNG increased serum MMP-9, while DOX decreased MMP-9 levels compared to PL after 1 month (p<.05). DOX decreased endometrial MMP-9 at 1 and 6 months compared to baseline and PL (p<.05). DOX increased endometrial TIMP-1 at 6 months compared with baseline and PL (p<.05). MMP-2 levels were unchanged. CONCLUSION: LNG SI increased serum MMP-9 and TIMP-1 levels, while DOX decreased both serum and endometrial MMP-9 levels.

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.

Rate of blastocyst development from excess embryos remaining in culture after day 3 embryo transfer.

OBJECTIVE: To assess the rate of blastocyst development (BDR) from embryos remaining in culture after day-3 embryo transfer (ET), and its relationship to cause of infertility. STUDY DESIGN: Retrospective cohort study in tertiary-care IVF Center. Blastocyst development rate (BDR) after day-3 ET was assessed in 126 women who underwent either conventional IVF or ICSI. RESULTS: Mean age, early follicular FSH levels, number of 2PN zygotes, number of excess embryos, and number of ET were similar between patients that underwent IVF and ICSI. Overall, 20% of extra embryos from conventional IVF patients developed into blastocysts compared to 14% of embryos obtained from ICSI. Cause of infertility did not affect BDR, even in patients who required ICSI due to male factors. CONCLUSIONS: Low rates of blastocyst development from excess embryos are similar between IVF and ICSI patients. Only 15 to 25% of excess embryos left in culture develop into blastocysts, regardless of cause of infertility. Physicians and patients can use this information to adjust both AR treatment protocols and patient expectations.

High rates of embryo wastage with use of assisted reproductive technology: a look at the trends between 1995 and 2001 in the United States.

OBJECTIVE: To determine what percentage of embryos achieved through assisted reproductive technology (ART) do not result in a live birth and to examine the relationships among the number of embryos transferred, infants delivered, and embryos wasted. DESIGN: Retrospective correlational study of the U.S. summary data of ART results for the years of 1995-2001. PATIENTS: Fertility clinics reporting data to the Society of Assisted Reproductive Technology (SART). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistics for ART cycles using fresh, nondonor eggs and embryos were derived, and the percentage of embryos wasted each year was calculated. Trends over time were evaluated for percent embryos wasted, the average number of embryos transferred, and the delivery per transfer rate. Correlations between these variables were analyzed. RESULT(S): The percentage of embryos transferred that did not produce a live birth was 90.8 in 1995 and decreased to 84.9 in 2001. This trend significantly correlated with a reduction in the number of embryos transferred (from 3.9 to 3.1) and with an improvement in delivery rate per transfer (25% to 33.4%). CONCLUSION(S): The vast majority of embryos produced in vitro and transferred fail to develop into an infant, supporting the concept that only a small fraction of embryos has the capacity to become a live birth. Clinicians should strive to reduce embryonic wastage without an adverse effect on delivery rates by perfecting methods of ovarian stimulation and embryo screening, and by transferring fewer embryos.

Female sexual dysfunction and use of hormone therapy in postmenopausal women.

Sexual dysfunction is a common problem for women of all ages and remains an important aspect of women's health following menopause. For postmenopausal women, the evaluation and management of sexual dysfunction differs from that of younger women because the etiology is often linked to the diminished levels of sex hormones. Female sexual function is highly complex and deeply influenced by nonhormonal factors such as emotional intimacy and culture. Our understanding of this important area of women's health remains inadequate, and much more research needs to be performed before definitive conclusions can be made. Existing data allow for some preliminary observations. It appears that lack of estrogen may lead to sexual dysfunction primarily by causing vaginal atrophy and dyspareunia. These symptoms may be treated by systemic or local estrogen therapy. Conversely, androgen deficiency appears to be most strongly linked to diminished sexual desire. Growing evidence indicates that administration of androgens may be beneficial in such situations. Other agents that use sex hormone receptors, such as selective estrogen receptor modulators and tibolone, also may affect sexual function.

Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis.

BACKGROUND: Recurrent pregnancy loss (RPL) is a significant clinical problem. Recently, thrombophilias have been implicated as a possible cause. Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are the most common types of hereditary thrombophilias, but are usually undiagnosed because most carriers are asymptomatic. The relationship between FVL, G20210A, and RPL has been investigated with conflicting results. This study analyzed existing data to determine whether an association exists. METHODS: A systematic review of the literature was performed. Only case-control studies that defined RPL as 2 or more pregnancy losses in the first or second trimester and that confirmed mutations by DNA analysis were included. Sixteen studies were selected for the FVL meta-analysis and 7 for the G20210A analysis. Stratified and multivariate logistic regression analyses were performed with the use of aggregate data. Results were confirmed by means of fixed- and random-effects meta-analyses models. RESULTS: The combined odds ratios for the association between RPL and FVL and between RPL and G20210A were 2.0 (95% confidence interval, 1.5-2.7; P<.001) and 2.0 (95% confidence interval, 1.0-4.0; P =.03), respectively. Similar results were produced by the logistic regression and both fixed- and random-effects meta-analysis models. CONCLUSIONS: Carriers of FVL or prothrombin gene mutations have double the risk of experiencing 2 or more miscarriages compared with women without thrombophilias. Hereditary thrombophilias may be an unrecognized cause of RPL. We recommend testing for these mutations in women with RPL.