A two- versus three-embryo transfer: the oocyte donation model.

OBJECTIVE: To compare implantation and pregnancy rates in oocyte recipients undergoing a two-embryo versus three-embryo transfer, 3 days after retrieval. DESIGN: Retrospective comparative analysis. SETTING: University-based in vitro fertilization center. PATIENT(S): All oocyte recipients undergoing embryo transfer from January 1, 1997 through August 31, 1999. INTERVENTION(S): Recipients received two or three embryos. MAIN OUTCOME MEASURE(S): Implantation, and clinical and multiple pregnancy rates. RESULT(S): Seventy-three recipients underwent a two-embryo transfer, and 376 had three embryos replaced. The numbers of oocytes retrieved (12.7 +/- 0.89 vs. 13.1 +/- 0.36) and embryos obtained (8.05 +/- 0.65 vs. 8.77 +/- 0.27) did not differ between the two-embryo and three-embryo transfer groups, nor did the proportion of patients with embryo cryopreservation (54.3% vs. 42.6%, respectively). There was no significant difference in pregnancy or implantation rates when comparing those patients with a two-embryo transfer to those with a three-embryo transfer. Significantly, 13.8% of the pregnancies in the three-embryo transfer group were triplet. CONCLUSION(S): Reducing the number of embryos transferred in an oocyte donation cycle can lower the incidence of triplet pregnancies without significantly lowering the overall pregnancy rate.

Fertility after hysteroscopic resection of submucous myomas.

STUDY OBJECTIVE: To analyze fertility outcomes after resection of submucous myomas by operative hysteroscopy in infertile women. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: Academic tertiary referral center. PATIENTS: Forty-one women (age 28-42 yrs) old with primary and secondary infertility, and histologically proved submucous myomas. Intervention. Hysteroscopic myomectomy performed with a rigid resectoscope. MEASUREMENTS AND MAIN RESULTS: Of the 41 patients, 25 (60.9%) became pregnant overall and 20 (48.7%) delivered at term. Seventeen patients delivered a single fetus. Five delivered twins, three at term and two at 33 and 35 weeks. One woman delivered triplets at 31 weeks. The total delivery rate was 56.0%. Two women miscarried, at 6 and 8 weeks. One patient developed postoperative Asherman's syndrome. CONCLUSION: Our results indicate that hysteroscopic myomectomy improves fertility in previously infertile women. Resection is a viable alternative to abdominal myomectomy for submucous myomas. (J Am Assoc Gynecol Laparosc 6(2):155-158, 1999)

Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study.

OBJECTIVE: To evaluate the efficacy of oral micronized progesterone compared with IM progesterone in oil for luteal support in patients undergoing IVF who are treated with a GnRH agonist. DESIGN: Randomized prospective clinical trial. SETTING: University-based IVF center. PATIENT(S): Women <40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation. INTERVENTION(S): Patients were randomized to receive either oral micronized progesterone (200 mg three times daily) or IM progesterone (50 mg daily). MAIN OUTCOME MEASURE(S): Progesterone levels at standardized days 21 and 28, and pregnancy and embryo implantation rates. RESULT(S): Day 21 progesterone levels were 77.6+/-13.2 ng/mL in the IM group and 81.5+/-16.2 ng/mL in the oral group. Day 28 progesterone levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral group. The clinical pregnancy rates were 57.9% and 45.8% for the IM and oral groups, respectively. The implantation rate per embryo was significantly higher in the IM group (40.9%) than in the oral group (18.1%). CONCLUSION(S): When used according to our protocols, oral progesterone and IM progesterone result in comparable levels of circulating progesterone. However, oral progesterone results in a reduced implantation rate per embryo.

Genetic screening of prospective oocyte donors.

OBJECTIVE: To report our experience with genetic screening of oocyte donor candidates and to determine the frequency with which significant genetic issues are identified. DESIGN: Prospective genetic screening of oocyte donor candidates. SETTING: University hospital oocyte donation program. PATIENT(S): Women presenting consecutively as volunteer oocyte donors. INTERVENTION(S): Genetic screening was performed by pedigree analysis and laboratory studies. MAIN OUTCOME MEASURE(S): Inclusion in the oocyte donor pool based on the results of clinical evaluation and laboratory tests consisting of polymerase chain reaction based mutational analysis for cystic fibrosis carrier status, cytogenetic analysis for karyotype, enzymatic assay for Tay-Sachs disease carrier status, and complete blood count and hemoglobin electrophoresis. RESULT(S): Eight (11%) of 73 oocyte donor candidates were excluded from the donor pool because of a potentially serious genetic finding. Cystic fibrosis mutations were identified in 5 candidates (7%), abnormal karyotypes were found in 2 (3.5%), and an autosomal dominant skeletal dysplasia was identified in 1 (1.4%). CONCLUSION(S): A significant proportion of women who present as candidates for oocyte donation are inappropriate for donation because of their genetic history or genetic testing results. A thorough genetic evaluation, including a history and laboratory screening, is essential to any oocyte donation program to maximize positive outcomes in pregnancies achieved through assisted means.

Preimplantation genetic diagnosis of human embryos for Marfan's syndrome.

PURPOSE: Single-cell nested polymerase chain reaction (PCR) and Ddel endonuclease digestion were used to detect the presence of a Marfan's syndrome mutation in human preimplantation embryos derived from in vitro fertilization (IVF). These procedures were conducted to eliminate the possibility of transmission of the affected allele from the father to his offspring. The mutation on chromosome 15 is transmitted as an autosomal dominant trait, and the chance of having a child affected with the disease is 50%. METHODS: A couple presented to the Program for In Vitro Fertilization, Reproductive Surgery and Infertility for preimplantation genetic diagnosis. IVF was performed and embryo biopsy was done on day 3 embryos. Single blastomeres were removed from embryos and subjected to nested PCR analysis and endonuclease digestion to detect a Marfan's syndrome mutation located on chromosome 15 inherited from the father. RESULTS: Thirteen oocytes were injected with spermatozoa using intracytoplasmic sperm injection, and nine fertilized normally. Following embryo biopsy and polymerase chain reaction amplification-Ddel endonuclease digestion, five embryos were detected that were positive for the mutation. The four non-affected embryos were transferred to the uterus, resulting in a healthy and normal ongoing pregnancy.

Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients.

OBJECTIVE: To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients. DESIGN: Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery. SETTING: Prospective randomized trial at a university-based hospital. PATIENTS: The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes. MAIN OUTCOME MEASURES: Development of postpartum endomyometritis. RESULTS: The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered. CONCLUSION: Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.

Midfollicular anticardiolipin and antiphosphatidylserine antibody titers do not correlate with in vitro fertilization outcome.

OBJECTIVE: To determine the prevalence of anticardiolipin and antiphophatidylserine antibodies in an IVF population and to correlate their presence and specific isotype with IVF cycle outcome. DESIGN: Retrospective clinical study using stored midfollicular sera for determination of antibody status. SETTING: University hospital infertility clinic. PATIENT(S): Women who underwent IVF treatment in 1991. INTERVENTION(S): Midfollicular sera were used to assess antibody status during the time of stimulation for IVF. MAIN OUTCOME MEASURE(S): Anticardiolipin and antiphosphatidylserine antibody titers and biochemical or sonographic documentation of IVF cycle outcome. RESULT(S): The overall prevalence of anticardiolipin and antiphosphatidylserine antibodies in IVF patients was 7.0% and 11.2%, respectively. There was no statistically significant difference in the prevalence of these antibodies in the groups of patients with a biochemical pregnancy (0 for anticardiolipin and 2.8% for antiphosphatidylserine), spontaneous miscarriage (11.4% for anticardiolipin and 20% for antiphosphatidylserine), ongoing pregnancy (7.3% for anticardiolipin and 11.6% for antiphosphatidylserine), and patients who failed to conceive (7.2% for anticardiolipin and 10.8% for antiphosphatidylserine). There was no correlation between outcome and the antibody isotype expressed. CONCLUSION(S): Anticardiolipin and antiphosphatidylserine antibodies are poorly predictive of the IVF cycle outcome. Routine testing of IVF patients for the presence of these antibodies is of limited clinical utility.

Variability of day 3 follicle-stimulating hormone levels in eumenorrheic women.

OBJECTIVE: To assess the intercycle variability of early follicular follicle-stimulating hormone (FSH) and estradiol (E2) levels in eumenorrheic women according to age. STUDY DESIGN: Forty-eight female volunteers with regular menstrual cycles were studied. Serum samples were obtained on cycle day 3 in multiple cycles over a one-year period. Serum was also obtained on consecutive cycle days 2, 3 or 4 in a single cycle in 20 participants. All samples were assayed for FSH and E2 by radioimmunoassay. RESULTS: In women under 40 years of age, all initial day 3 FSH levels were < 20 mIU/mL, and 15% of subjects had a subsequently elevated day 3 FSH level (> or = 20 mIU/mL) within the year. In eight women 40-44 years of age, 75% had an initial day 3 FSH level < 20 mIU/mL, but half of them subsequently had an elevated level, > 20 mIU/mL, within the year. Between cycle days 2, 3 and 4, FSH (coefficient of variation [CV] = 14.8%, 95% confidence interval (CI) = 11.4-18.3%) varied less than E2 (CV = 31.1%, 95% CI = 21.5-40.6%). CONCLUSION: A single day 3 FSH level < 20 mIU/mL is highly predictive of all subsequent values within a year and occurred only in women under 40. An FSH level drawn on cycle day 2 or 4 will probably be within 18% of the day 3 value, but the E2 level may vary by up to 40%.

Comparison of three regimens recommended by the Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic inflammatory disease.

This six-center, prospective, open-label clinical trial compared the efficacy and safety of three regimens recommended by the Centers for Disease Control and Prevention (CDC) for the treatment of women hospitalized for acute pelvic inflammatory disease (PID). The study focused on the response to inpatient therapy, not on long-term prevention of sequelae. A severity score was used for objective comparison of the degree of illness before and after therapy. Women were randomly assigned (in a 1:1:1 ratio) to treatment with cefoxitin plus doxycycline, clindamycin plus gentamicin, or cefotetan plus doxycycline. Two hundred seventy-five (94.2%) of 292 evaluable women required no alteration in therapeutic regimen. The three regimens produced almost identical cure rates. No serious adverse clinical or laboratory events were observed. In short, the three regimens recommended by the CDC for inpatient therapy of acute PID were similarly effective and safe.

Epididymal micropuncture with in vitro fertilization and oocyte micromanipulation for the treatment of unreconstructable obstructive azoospermia.

OBJECTIVE: To provide fertility to couples in whom the man has surgically unreconstructable obstructive azoospermia. DESIGN: Prospective. SETTING: Hospital-based IVF unit, including associated division of urologic microsurgery. PATIENTS: Couples referred to our fertility unit for treatment of men with surgically unreconstructable reproductive tract obstruction, including congenital absence of the vas deferens. MAIN OUTCOME MEASURES: Fertilization, pregnancies, and live births. RESULTS: Of 51 cycles in which sperm and eggs were retrieved, 67% (34/51) resulted in fertilization and 27.5% (14/51) developed clinical pregnancy. Clinical pregnancy rate per couple was 33% (14/43). A total of 15 live births have been obtained in 11 couples with one ongoing pregnancy. Epididymal length was the best predictor of sperm quality and pregnancy results. For couples with at least the corpus epididymis present, 41% (9/22) of cycles resulted in clinical pregnancies. CONCLUSIONS: Pregnancy rates are optimized using sperm retrieved from the epididymis by micropuncture and when micromanipulation is available for use during IVF.

Improved pregnancy outcome with gonadotropin releasing hormone agonist (GnRH-a) stimulation is due to the improvement in oocyte quantity rather than quality.

The impact of gonadotropin releasing hormone agonist (GnRH-a) on the quality and quantity of oocytes harvested in in vitro fertilization-embryo transfer (IVF-ET) patients was studied by comparing the results for patients stimulated with gonadotropin alone and with gonadotropin plus GnRH-a. Adding GnRH-a significantly improved the viable pregnancies per transfer and reduced the spontaneous abortions, which seemed to improve oocyte quality. However, when oocyte quality was evaluated by the fertilization rate and the implantation and delivery rates per embryos transferred, there were no significant difference in the results, indicating that GnRH-a did not improve the oocyte quality. On the other hand, GnRH-a significantly increased the average number of oocytes harvested, fertilized, and transferred, and this increased number of oocytes transferred has been demonstrated to increase pregnancy and multiple-pregnancy rates. Multiple pregnancy with more embryos implanted would significantly reduce the abortion rate. Abortion rates decreased inversely to the number of embryos implanted. Our data strongly suggest that the efficacy of GnRH-a on IVF-ET patients was due more to the quantity increase than the quality of embryos transferred.

Discordance of müllerian agenesis in monozygotic twins. A case report.

With the case described here there have been six reported cases of discordance of müllerian development in monozygotic twins. The etiology of the disorder remains obscure. Although a genetic basis may exist in some cases, it could not be demonstrated in any of the six cases.

Evaluation of leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins for in vitro fertilization or gamete intrafallopian transfer.

A prospective randomized trial was conducted to compare the efficiency of two ovarian stimulation protocols for in vitro fertilization-embryo transfer or gamete intrafallopian transfer. Protocol 1 consisted of clomiphene citrate and human menopausal gonadotropin (hMG) with 55 cycles of 42 patients being evaluated. Protocol 2 had 38 cycles of 34 patients receiving a gonadotropin-releasing hormone agonist (GnRH-a) and hMG. The incidence of a spontaneous luteinizing hormone surge was 38.2% in protocol 1 and 0% in protocol 2. Both protocols had a similar cancellation rate. The total clinical pregnancy rates per oocyte retrieval for patients receiving protocol 1 and protocol 2 were 19.5% and 10.3%, respectively. The difference was not statistically significant. Therefore, as first-line ovulation induction agents, it cannot be concluded that either protocol demonstrates a clear superiority over the other and further trials of the GnRH-a/hMG combination are indicated.

Cefotaxime for cesarean section prophylaxis in labor. Intravenous administration vs. lavage.

To compare the efficacy of antibiotic prophylaxis through uterine lavage in women undergoing cesarean section in labor to the efficacy of the more standard, perioperative intravenous method, we prospectively randomized 100 women to receive either 2 g of cefotaxime in 1,000 mL of normal saline with a lavage protocol or 1 g of cefotaxime intravenously after cord clamping followed by 1-g doses 6 and 12 hours later. The two groups were similar with respect to age, gestational age, race, weight, length of labor and of ruptured membranes, use of internal monitoring, blood loss and number of vaginal examinations. Standard febrile morbidity and postpartum endomyometritis requiring antibiotic therapy occurred in 18% and 12%, respectively, of the lavage group and in 16% and 12%, respectively, of the intravenous group. Before the routine use of prophylactic antibiotics for cesarean section in labor on our service, the febrile morbidity and endomyometritis rates were 36% and 32%, respectively. The results confirm the benefit of prophylactic antibiotics for cesarean section in labor and demonstrate that the lavage and intravenous methods are similar with respect to efficacy.

Relationship between menarcheal age and adult height.

Many factors contribute to the attainment of adult height, including genetic and environmental variables. To assess the relationship between menarcheal age and adult height, measured adult height and recalled menarcheal age were compared by regression analysis in 425 women. The overall regression equation, Height = 158.14 + .4321 (Age) - .1667 (Age - 13)2, was significant (P less than .003), as was the coefficient for the quadratic term (P not equal to .014). After exclusion of those in whom menarche occurred after age 16, the overall linear regression equation for the remaining 416 patients, Height = 153.95 + .7353 (Age), was still significant (P not equal to .001), but the coefficient for the quadratic term was not. These data suggest that menarcheal age significantly correlates with adult height as an independent variable.

The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies.

Five regularly menstruating women of proven fertility, with normal prolactin and thyroid function studies, underwent a total of 39 endometrial biopsies (EMBs). The slides were dated in blinded fashion, and the cycle date determined by considering the date of the next menstrual period as day 28 and counting backward. Using a 2-day or greater lag in endometrial maturity to define a luteal phase defect (LPD), the incidence of single and sequential out-of-phase EMBs was 51.4% and 26.7%, respectively. Using a 3-day or greater lag to define a LPD, the incidence of single and sequential out-of-phase EMBs was 31.4% and 6.6%, respectively. These incidences in normal, fertile women are as high as the rates quoted for infertile populations, and call into question the standard criteria for defining this condition and evaluating therapies to correct it.

Comparative effectiveness and safety of cefotetan and cefoxitin as prophylactic agents in patients undergoing abdominal or vaginal hysterectomy.

In a multicenter, randomized clinical trial, 282 women who underwent abdominal or vaginal hysterectomy were given a single preoperative 2 g dose of cefotetan (171 evaluable patients) or three perioperative 2 g doses of cefoxitin (84 evaluable patients) as antibiotic prophylaxis. A successful clinical response occurred in 92 percent of those receiving cefotetan and 90 percent of those receiving cefoxitin who underwent abdominal hysterectomy, and in 94 percent of those receiving cefotetan and 93 percent of those receiving cefoxitin who underwent vaginal hysterectomy. The incidence of vaginal cuff cellulitis was 3.4 percent and 5 percent for cefotetan and cefoxitin patients, respectively, who underwent abdominal hysterectomy, and 4.8 percent and 4.5 percent, respectively, for those who underwent vaginal hysterectomy. The incidence of major wound infection was 3.4 percent and 2.5 percent for cefotetan and cefoxitin, respectively, in the abdominal hysterectomy group. Postoperative changes in oral body temperature, duration of hospitalization, and postoperative grading of surgical wounds were similar. Both drugs were well tolerated. These results suggest that a single dose of cefotetan is equally effective and as safe as multiple-dose cefoxitin for prophylaxis in patients undergoing hysterectomy.

Comparison of cefotetan and cefoxitin prophylaxis for abdominal and vaginal hysterectomy.

The safety and efficacy of parenteral prophylaxis with either cefotetan or cefoxitin were evaluated in a prospective, randomized study of 355 subjects undergoing abdominal or vaginal hysterectomy. Each subject received either a single 1 gm dose of cefotetan intravenously 30 to 60 minutes before operation or three 2 gm doses of cefoxitin, the first 30 to 60 minutes before operation and subsequent doses 6 and 12 hours later. Prophylaxis was successful in 69 of 70 (98.6%) receiving cefotetan and 32 of 33 (97.0%) receiving cefoxitin who underwent vaginal hysterectomy. Prophylaxis was successful in 160 of 169 (94.7%) receiving cefotetan and in 79 of 83 (95.2%) receiving cefoxitin who underwent abdominal hysterectomy. Both drugs were well tolerated and without serious side effects or complications. On the basis of these findings, we conclude that a single 1 gm dose of cefotetan given before operation is as safe and effective as a multiple-dosing regimen of cefoxitin in subjects undergoing vaginal hysterectomy and in those undergoing abdominal hysterectomy at institutions where prophylaxis is indicated.