A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET. DESIGN: Randomized, open-label study. SETTING: Academic medical center. PATIENT(S): Two hundred and one women undergoing IVF-ET. INTERVENTION(S): Women were randomized to supplementation with Crinone 8% (90 mg once daily) or IM progesterone (50 mg once daily) beginning the day after oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy, embryo implantation, and live birth rates. RESULT(S): The women randomized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy (48.5% vs. 30.4%; odds ratio [OR], 2.16; 95% confidence interval [CI], 1.21, 3.87), embryo implantation (24.1% vs. 17.5%; OR, 1.89; 95% CI, 1.08, 3.30), and live birth rates (39.4% vs. 24.5%; OR, 2.00; 95% CI, 1.10, 3.70) than women randomized to Crinone 8%. CONCLUSION(S): In women undergoing IVF-ET, once-a-day progesterone supplementation with Crinone 8%, beginning the day after oocyte retrieval, resulted in significantly lower embryo implantation, clinical pregnancy, and live birth rates compared with women supplemented with IM progesterone.

Phytoestrogen supplementation and endometrial cancer.

BACKGROUND: Phytoestrogens are increasingly used by patients as "natural" alternatives to hormone replacement. Attention in scientific and lay literature has focused on their potential to prevent menopausal symptoms, bone loss, heart disease, or breast cancer. Less is known about effects on the endometrium, specifically, whether prolonged exposure to phytoestrogens could promote hyperplasia or neoplasia, as does unopposed estrogen. CASE: We report the case of a woman diagnosed with grade 1 endometrioid adenocarcinoma of the endometrium whose history was notable for extensive use of supplemental phytoestrogens. CONCLUSION: The effects of phytoestrogens on endometrial tissue are not known. Given their increasing popularity and availability in concentrated form as dietary supplements, additional research is warranted before we can counsel our patients regarding the safety of such supplements.

In vitro fertilization for cancer patients and survivors.

OBJECTIVE: To determine in vitro fertilization (IVF) outcome in cancer patients. DESIGN: Retrospective record review. SETTING: Academic, hospital-based assisted reproductive technology (ART) program. PATIENT(S): Sixty-nine women undergoing 113 IVF/gamete intrafallopian transfer (GIFT) cycles after cancer treatment in one partner, and 13 women undergoing 13 IVF cycles for embryo cryopreservation before chemotherapy/radiation. INTERVENTION(S): IVF, intracytoplasmic sperm injection (ICSI), assisted hatching, and gamete intrafallopian transfer as indicated. MAIN OUTCOME MEASURE(S): Delivery rate, spontaneous abortion rate, number of embryos cryopreserved, cancer diagnosis, systemic or local cancer treatment, female age, amount of gonadotropin used, treatment duration, peak estradiol level, and number of oocytes and embryos. RESULT(S): The women undergoing IVF after chemotherapy had poorer responses to gonadotropins than did the women with locally treated cancers even though they were younger (33.5 +/- 1.3 vs. 36.5 +/- 0.5 years; P<.05). The delivery rates after the women had undergone chemotherapy tended to be lower among the systemic treatment group than it was for the local cancer treatment group: (13.3% [2 of 15] vs. 40% [14 of 56, P=NS]). The women who had cryopreserved all embryos before chemotherapy produced more oocytes (18.7 +/- 3.2 vs. 14.5 +/- 1.2) and embryos (11.3 +/- 1.9 vs. 7.5 +/- 0.7) than did the women who had had a history of local cancer treatment. Male factor infertility as a result of cancer treatment is well treated with IVF or intracytoplasmic sperm injection, where indicated (32% delivery rate/cycle), with no difference between the frozen sperm banked before cancer treatment and fresh sperm produced after treatment. CONCLUSION(S): Chemotherapy diminishes the response to ovulation induction in assisted reproductive technologies. IVF with cryopreservation of embryos allows embryo banking before chemotherapy for women who have been newly diagnosed with cancer. Factors related to the partner affect the success of IVF for male factor infertility as a result of cancer treatment.

Transcervical placement of a Malecot catheter after hysteroscopic evaluation provides for easier entry into the endometrial cavity for women with histories of difficult intrauterine inseminations and/or embryo transfers: a prospective case series.

OBJECTIVE: To evaluate a new technique designed to improve access to the endometrial cavity through tortuous and/or stenotic endocervical canals in women with histories of difficult IUIs, ETs, or endometrial biopsies. DESIGN: Prospective case series. SETTING: Tertiary care center. PATIENT(S): Women with histories of difficult intrauterine procedures because of tortuous and/or stenotic endocervical canals who continued to undergo treatment. INTERVENTION(S): Hysteroscopic evaluation and/or correction of the endocervix, followed by transcervical placement of a Malecot catheter (CR Bard Inc., Covington, GA) for an average of 10 days. MAIN OUTCOME MEASURE(S): Improvement in the ease of access to the endometrial cavity during IUIs or ETs. RESULT(S): Thirty-two of 36 patients had significantly easier procedures after the placement and removal of a Malecot catheter. CONCLUSION(S): Hysteroscopic evaluation and placement of a Malecot catheter is a useful technique that allows easier entry through the cervical canal in patients in whom previous IUIs, ETs, and endometrial biopsies have been difficult. This procedure may lead to improved pregnancy rates, particularly with IVF-ET, as the ease of ET has been correlated with improved implantation rates.

Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates in in vitro fertilization cycles: a prospective, case-controlled study.

PURPOSE: The effect of endometriomas on oocyte quality, embryo quality, and pregnancy rates in in vitro fertilization (IVF) cycles was evaluated. METHODS: Forty-five women had "chocolate" cysts aspirated at the time of oocyte retrieval, and cyst fluid CA 125 levels were measured to ascertain presence of "true" endometriomas. Fifty-seven women without any complex cysts at the time of oocyte retrieval served as controls. IVF cycle outcome parameters were compared between the two groups. RESULTS: Women with endometriomas experienced a significantly higher rate of early pregnancy loss compared to controls (47 vs 14%). There was also a trend toward fewer oocytes retrieved and fewer embryos reaching at least the four-cell stage 48 hr after retrieval in patients with true endometriomas vs controls. CONCLUSIONS: The presence of endometriomas at the time of oocyte retrieval is associated with increased rates of early pregnancy losses. The number of oocytes retrieved and the embryo quality may also be affected adversely in the presence of endometriomas.

Is leukocytospermia clinically relevant?

OBJECTIVE: To evaluate the relationship between seminal leukocytes and abnormal semen parameters in a large population of infertility patients. DESIGN: Prospective clinical study. SETTING: Center for Reproductive Medicine at Brigham and Women's Hospital, Boston, Massachusetts. PATIENT(S): One thousand seven hundred ten male partners in infertile couples attending the Center for Reproductive Medicine. MAIN OUTCOME MEASURE(S): Seminal leukocyte concentrations, sperm count, motility and morphology, and the prevalence of samples with < 10 x 10(6) motile sperm per ejaculate (a parameter defined by IVF as the most clinically significant predictor of male infertility). RESULT(S): There was a strong relationship between increasing leukocyte concentrations in semen and abnormal semen parameters. Statistically significant differences in sperm concentrations and morphology were observed at leukocytospermia thresholds of 5 x 10(5) and 2 x 10(6) granulocytes/mL, respectively. The percentage of suboptimal semen specimens as defined by IVF criteria (< 10(7) total motile sperm per ejaculate) significantly increased with increasing seminal granulocyte concentrations. A twofold increased prevalence in such suboptimal semen specimens was observed at the leukocytospermia threshold of 2 x 10(6) granulocytes/mL. CONCLUSION(S): There is a relationship between increasing seminal granulocyte concentrations and poor semen parameters. At seminal granulocyte concentrations > 2 x 10(6)/mL, semen parameter abnormalities were observed that were both statistically and clinically significant.

Localization of small ovarian Sertoli-Leydig cell tumors by transvaginal sonography with color Doppler.

Color Doppler ultrasound is a non-invasive diagnostic modality that has been gaining popularity in the evaluation of gynecological tumors. It demonstrates blood flow in a visually familiar way, and facilitates detection of neovascularity in pelvic tumors. In this article we describe, for the first time, a case in which a small androgen-producing ovarian tumor was localized by color Doppler ultrasound after other non-invasive imaging techniques failed.

Antibiotic therapy and leukocytospermia: a prospective, randomized, controlled study.

OBJECTIVE: To determine the efficacy of common antibiotic therapies for treatment of leukocytospermia of unknown etiology. DESIGN: Prospective, randomized, controlled clinical study. SETTING: Fertility and Endocrinology Unit at Brigham and Women's Hospital, Boston, Massachusetts. PATIENTS: One thousand seven hundred ten male partners in infertile couples attending the Fertility and Endocrinology Unit. INTERVENTIONS: Concentrations of seminal peroxidase-positive granulocytes were determined during all routine semen analyses performed over a 30-month period. Of 119 men found to have leukocytospermia (> 10(6) granulocytes/mL semen) on first visit, 54 agreed to be randomized into one of three groups, and 41 patients completed the study. Group I (n = 13) and their wives received a 14-day course of oral doxycycline, 100 mg twice per day. Group II (n = 11) and their wives received a 14-day course of oral trimethoprim 160 mg-sulfamethoxazole 800 mg twice per day. Group III (n = 17) and their wives received no therapy. Four weeks after randomization, repeat semen analyses and granulocyte quantitations were done. RESULTS: Neither of the antibiotic regimens resulted in a significantly higher rate of resolution of leukocytospermia over that seen in the control group. CONCLUSIONS: There is a high rate of spontaneous resolution of leukocytospermia after one positive test. Antibiotics are no more beneficial than no therapy for treatment of this condition.

The effects of cytokines on human chorionic gonadotropin (hCG) production by a trophoblast cell line.

The present study was conducted to investigate the effects of cytokines on human chorionic gonadotropin (hCG) and its alpha- and beta-subunit release as well as protein synthesis in a trophoblast cell line. The human choriocarcinoma cell line, Jar, was used as a trophoblast model. Jar cells were incubated for 24 h with varying concentrations (5 x 10(-4)-40 micrograms/ml) of the following cytokines: Il-1, Il-2, Il-3, Il-4, Il-5, Il-6, IFN-gamma, tumor necrosis factor (TNF)-alpha, M-CSF and GM-CSF. Supernatants were assayed for hCG and its alpha- and beta-subunits by immunoradiometric methods. Cytotoxic effects were assessed by trypan blue staining. Protein synthesis was measured by [3H]leucine incorporation. The cytokines Il-1 and TNF-alpha significantly stimulated hCG release. The other cytokines had no significant effect on hCG production. Protein synthesis by the Jar cells was not significantly affected by either Il-1 or TNF-alpha. However, IFN-gamma (40 micrograms/ml) significantly suppressed protein synthesis by the Jar cells. Trophoblast viability in the presence of TNF-alpha (10 micrograms/ml) and IFN-gamma (40 micrograms/ml) was only 40% and 50%, respectively. These results suggest that cytokines may be important regulators of trophoblast function. Il-I appears to have a stimulatory effect on trophoblast hCG release, while TNF-alpha and IFN-gamma appear to have cytotoxic effects on trophoblast cells.

Ruptured pelvic abscess after intrauterine insemination: a case report.

This case reports a serious but previously unreported complication of IUI. Further reports of serious infection would warrant consideration of antibiotic prophylaxis in some cases.