Bradley J. Van Voorhis

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization

OBJECTIVE To determine prognostic factors for achieving a pregnancy with intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost-effectiveness of IUI and IVF based on semen analysis results. DESIGN Retrospective cohort study. SETTING Academic university hospital-based infertility center. PATIENT(S) One thousand thirty-nine infertile couples undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples undergoing 551 IVF cycles. INTERVENTION(S) IUI and IVF treatment. MAIN OUTCOME MEASURE(S) Multiple logistic regression analysis was used to assess the significance of prognostic factors including a womans age, gravidity, duration of infertility, diagnoses, use of ovulation induction, and sperm parameters for predicting the outcomes of clinical pregnancy and live birth rate after the first cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these treatments were then determined based on sperm count results. RESULT(S) Female age, gravidity, and use of ovulation induction were all independent factors in predicting pregnancy after IUI. The average total motile sperm count in the ejaculate was also an important factor, with a threshold value of 10 million. For IVF, only female age was an important predictor for both clinical and ongoing pregnancy. When the average total motile sperm count was under 10 million, IVF with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S) An average total motile sperm count of 10 million may be a useful threshold value for decisions about treating a couple with IUI or IVF.

Natural history of uterine polyps and leiomyomata

OBJECTIVE To estimate the incidence and regression rates of uterine leiomyomata and polyps in a cohort of asymptomatic, premenopausal women. METHODS Saline infusion sonography was performed twice, 2.5 years apart, in a cohort of 64 initially asymptomatic women. Subjects completed a questionnaire that assessed the development of abnormal uterine bleeding. RESULTS The mean age of women (at second ultrasound) was 44 years. In four of seven women with polyps at the original ultrasound, their polyps regressed. Polyps that regressed tended to be smaller than polyps that persisted. Ten women had endometrial polyps at the second ultrasound for a point prevalence of 16% and a cumulative incidence rate of 12% per 2.5 years. A higher percentage of women with uterine polyps had complaints of abnormal uterine bleeding than women with no uterine abnormalities (70% versus 33%, P = .04). Six leiomyomata in four women were no longer detected in the second ultrasound. Leiomyomata that regressed were in older premenopausal women and were smaller than leiomyomata that persisted. The point prevalence and incidence rates of leiomyomata were 27% and 13% per 2.5 years, respectively. Leiomyomata grew an average of 1.2 cm per 2.5 years, but great variation in growth rates were noted. CONCLUSION Small uterine polyps frequently regressed spontaneously, whereas larger polyps were more likely to persist and were associated with the development of abnormal bleeding. Smaller leiomyomata in older premenopausal women also regressed whereas larger leiomyomata tended to grow while often remaining asymptomatic.

Sonohysterography in premenopausal women with and without abnormal bleeding

OBJECTIVE To estimate the prevalence of abnormalities detected by sonohysterography in premenopausal women who were asymptomatic or had abnormal uterine bleeding. METHODS Standard sonohysterography was done in 100 asymptomatic premenopausal women age 30 and older. The prevalence of uterine abnormalities was recorded and compared with findings in 80 premenopausal women evaluated in our unit for abnormal uterine bleeding. RESULTS Compared with asymptomatic women, premenopausal women with abnormal uterine bleeding had a higher prevalence of polyps (33 versus 10%), intracavitary myomas (21 versus 1%), and intramural myomas (58 versus 13%). Ten percent of asymptomatic women had polyps, but these polyps tended to be smaller than the polyps found in women with abnormal bleeding (8.5 versus 13.9 mm, P = .064). Polyps were associated significantly with myomas, and both were more common in older premenopausal women. CONCLUSION Intracavitary lesions and intramural myomas are more prevalent in women with abnormal uterine bleeding than in asymptomatic women, suggesting a causative relationship. However, small endometrial polyps are common and frequently asymptomatic.

Ovarian volume : a novel outcome predictor for assisted reproduction

OBJECTIVE To determine the potential of ovarian volume as a predictor of assisted reproduction outcomes. DESIGN Retrospective chart review. SETTING University-based assisted reproduction program. PATIENTS One hundred eighty-eight women initiating their first cycle of assisted reproduction. INTERVENTIONS None. MAIN OUTCOME MEASURES Pretreatment transvaginal ultrasound ovarian measurements were compared with subsequent ovulation induction parameters (peak E2, numbers of oocytes, and embryos) and cycle outcome (cancellation and pregnancy). RESULT Total ovarian volume and volume of the smallest ovary were significant variables predicting peak E2 and numbers of oocytes and embryos. Total ovarian volume was a predictor of cycle cancellation and volume of the smallest ovary a predictor of clinical pregnancy. Large ovarian volumes are associated with good assisted reproductive technology outcomes whereas small ovarian volumes are associated with poor outcomes. CONCLUSION Beyond maternal age, total ovarian volume, and volume of the smallest ovary are significant predictors of the success of assisted reproductive techniques.

The Effects of Smoking on Ovarian Function and Fertility During Assisted Reproduction Cycles

Objective To investigate the effects of cigarette smoking on ovarian function and fertility in women undergoing assisted reproduction cycles. Methods We assessed the effects of smoking on ovarian function and fertility in a cohort of 499 women. Questionnaires were designed to quantify past smoking exposure and to determine whether the woman was smoking during the treatment cycle. Ovarian function characteristics and pregnancy rates were compared among current smokers, past smokers, and nonsmokers. Results Compared with nonsmokers, both current and past smokers have reduced gonadotropin-stimulated ovarian function. A history of increasing tobacco exposure was associated with decreasing serum estradiol concentrations, numbers of retrieved oocytes, and numbers of embryos. On average, for every 10 pack-years of cigarette smoking, 2.5 fewer mature oocytes and 2.0 fewer embryos were obtained. Women who smoked during their treatment cycle had approximately a 50% reduction in implantation rate and ongoing pregnancy rate compared with women who had never smoked. Women who quit smoking before their treatment cycle had the same pregnancy rate as nonsmokers. Conclusion Cigarette smoking is associated with a prolonged and dose-dependent adverse effect on ovarian function. Smoking appears to have a more transient toxic effect on fertility, because current smokers, but not past smokers, had a markedly reduced pregnancy rate after treatment cycles compared with nonsmokers. Women should quit smoking before assisted reproduction cycles.

Detection of cesarean scars by transvaginal ultrasound

OBJECTIVE: To assess the ability of transvaginal ultrasound to detect cesarean scars and their defects in the nonpregnant state. METHODS: Asymptomatic, parous volunteers underwent transvaginal ultrasound of the cervix, uterus, and adnexa. Uterine measurements, the presence or absence of a cesarean scar, and the presence of a scar defect, defined as fluid within the scar, were recorded. All subjects completed a self‐report questionnaire regarding obstetric history. Sonographers and investigators were blinded to subject history. RESULTS: A total of 70 subjects were enrolled. Of these, 38 women had a prior vaginal delivery and 32 women a prior cesarean delivery. One woman with a bicornuate uterus and three cesarean deliveries was excluded from data analysis. Real‐time transvaginal ultrasound proved 100% sensitive (exact 95% confidence interval [CI] 88.8, 100) and 100% specific (exact 95% CI 90.7, 100). Stored image review had a sensitivity of 87% (exact 95% CI 70.2, 96.4) and a specificity of 100% (exact 95% CI 90.7, 100). Fluid was visualized within the scars of 13 of 31 subjects (42%) with a prior cesarean delivery. All 13 were found among the 23 subjects (56%) who had labored prior to cesarean delivery. Moreover, women with cesarean scar defects had a greater number of cesarean deliveries (P < .04) than women without scar defects. CONCLUSION: Transvaginal ultrasound is highly accurate in detecting cesarean hysterotomy scars. Cesarean scar defect, defined by the presence of fluid within the incision site, was more common when labor preceded cesarean delivery and with multiple cesarean deliveries. (Obstet Gynecol 2003; 101:61‐5.

Nitric oxide inhibits aromatase activity: Mechanisms of action

NO synthase is present in human ovarian granulosa-luteal cells and NO inhibits estradiol secretion by granulosa cells in culture. These findings suggest that NO is an autocrine regulator of ovarian steroidogenesis. The purpose of this investigation was to explore the mechanisms through which NO exerts an inhibitory effect on cytochrome P450 aromatase activity. To examine the effect of NO on aromatase mRNA levels, human granulosa-luteal cells were cultured in the presence or absence of the NO donor SNAP for 16 h. Using a probe for human aromatase, Northern blots revealed a 26% decrease in aromatase mRNA in cells exposed to SNAP. Because this modest decrease in mRNA is unlikely to explain a rapid and profound reduction in estradiol secretion that we have observed, we looked for direct effects of NO on cytochrome P450 aromatase activity. Aromatase activity was assayed in placental microsomes and granulosa-luteal cells by measuring the release of 3H2O from [1 beta-3H] androstenedione. NO (10(-4)-10(-3)M), added as a saturated saline solution, reduced aromatase activity by as much as 90% in a concentration-dependent, non-competitive manner. In contrast, carbon monoxide (CO), a gas known to bind to the heme iron in aromatase, had no effect on aromatase activity when added alone nor could CO reverse the NO-induced inhibition of aromatase. These data suggest that NO binding to the heme is insufficient to inhibit aromatase activity. NO has been reported to alter protein function by reacting with the sulfhydryl group of cysteines, forming a nitrosothiol group. Because a cysteine sulfhydryl group is thought to participate in the catalytic mechanism of all P450 enzymes, experiments were designed to test whether NO might inhibit aromatase via such a mechanism. Addition of increasing amounts of mercaptoethanol, a chemical with free sulfhydryl groups, blocked the NO-induced inhibition of aromatase in microsomes. N-Ethylmaleimide, a chemical which covalently modifies sulfhydryl groups, reduced aromatase activity in a concentration-dependent manner. We conclude that NO inhibits aromatase both by decreasing mRNA for the enzyme and by an acute, direct inhibition of enzyme activity. We hypothesize that the direct inhibition occurs as a result of the formation of a nitrosothiol on the cysteine residue adjacent to the heme in aromatase.

Detection of human immunodeficiency virus type 1 in semen from seropositive men using culture and polymerase chain reaction deoxyribonucleic acid amplification techniques

We have demonstrated that the polymerase chain reaction is a valid and sensitive technique for the detection of human immunodeficiency virus type 1 (HIV-1) proviral deoxyribonucleic acid (DNA) in human semen. The combination of extraction, polymerase chain reaction, and liquid hybridization techniques used in this study was sensitive to a level of detection of one HIV-1 infected cell in 100,000 (or 3 infected cells/test sample). In a series of matched peripheral blood mononuclear cells (PBMC) and semen cells from 25 HIV-1 seropositive homosexual men, HIV-1 DNA was detected by polymerase chain reaction in 23 of 25 PBMC samples and 1 of 25 semen samples. By coculture on mitogen-activated peripheral blood leukocyte target cells, 19 of 24 PBMC and 4 of 24 semen samples were positive for infectious HIV-1. Of the four culture-positive semen samples, three were negative for the proviral form of the virus in the polymerase chain reaction assay. These data indicate that HIV-1 infected cells are not as prevalent in semen as in the peripheral blood. Furthermore, they indicate that the classical polymerase chain reaction approach, which only detects HIV-1 proviral DNA (infected cells), is not sufficient for clinical screening programs whose goal is the detection of HIV-1-infected semen samples. Accurate semen analysis by polymerase chain reaction may require enrichment of the infected cell population and/or a reverse transcriptase step to enable detection of the infectious ribonucleic acid form of the virus.

Role, epidemiology, and natural history of benign uterine mass lesions.

IntroductionBoth major tissue types of the uterine corpus-the endometrium and the myometrium-can develop nonmalignant mass lesions, especially during a womans fertile years. Endometrial polyps, consisting of endometrial glands, fibrotic stroma, and central thick-walled vascular channels, protru

Establishment of a successful donor embryo program: medical, ethical, and policy issues

OBJECTIVE To determine how couples prefer to dispose of their extra embryos and to establish a donor embryo program for the treatment of infertile couples. DESIGN Cohort study. SETTING University-based IVF program. PATIENT(S) Patients (n = 365) with cryopreserved embryos in storage for >2 years and eight patients who desired donated embryos for transfer. INTERVENTION(S) An IVF ethics committee was formed to discuss the ethical and policy issues involved in starting an embryo donation program and to establish program guidelines. Couples with embryos cryopreserved for > or = 2 years were contacted to determine their desires for disposition of embryos. Potential recipients of donated embryos were identified in our clinic, and donated embryos were transferred to these patients. MAIN OUTCOME MEASURE(S) Desires for embryo disposition and pregnancy rates. RESULT(S) Most couples elected either to continue storage of their embryos for future use (44%) or to discard their embryos (34%). A minority elected to donate their embryos either to infertile couples (11%) or for research (10%). Eight couples have had donated embryos transferred, and four have conceived ongoing pregnancies. CONCLUSION(S) Although only a small percentage of couples are willing to donate their embryos, the resulting number of embryos for use is substantial. Transfer of donated embryos results in a high pregnancy rate and is a cost-effective treatment of infertility.