Benjamin Gocial

Antibodies to phospholipids and nuclear antigens in patients with repeated abortions

The frequency of positive tests for antibodies to nuclear antigens (antinuclear, deoxyribonucleic acid, Ro, La, Smith, and ribonucleoprotein) or to phospholipids was investigated in 82 patients with isolated repeated abortions. Patients with a positive antibody test (positive or negative deoxyribonucleic acid antibodies) appeared to be a separate subgroup of those with unexplained repeated abortions from those with antibodies to cardiolipin. A total of 13.1% of the 61 patients with unexplained repeated abortions had elevated levels of IgM and/or IgG anticardiolipin antibody, while none were found in patients with explained abortions (p < 0.1). Enzyme-linked immunosorbent assays for antibodies binding to other phospholipids suggested that sera from patients with repeated abortions who had the lupus anticoagulant contained antibodies that were most often of the IgG class with affinity for negatively charged phospholipids. Binding of IgG but not IgM antibodies to cardiolipin correlated closely with that to other negatively charged phospholipids. The use of clotting tests for the lupus anticoagulant to screen patients with repeated abortions for associated autoantibodies is likely to significantly underestimate the extent of this clinical problem.

Laparoscopic laser treatment of endometriosis with the Nd: YAG sapphire probe

Laparoscopic surgery with the Nd:YAG laser generator and a sapphire probe was performed in 43 women for relief of pain and/or infertility associated with endometriosis and in two other women for treatment of an asymptomatic adnexal enlargement. More than half of the patients had American Fertility Society endometriosis scores of stage III or IV. Results of uterosacral denervation for pain relief were excellent, and eight of 17 patients who were attempting pregnancy with follow-up for 6 months conceived. A touch technique, reduced smoke production, and delivery via a flexible fiber constitute advantages to the surgeon compared with carbon dioxide systems.

Outcome in 242 in vitro fertilization-embryo replacement or gamete intrafallopian transfer-induced pregnancies

Two centers combined data on 152 in vitro fertilization embryo replacement and 90 gamete intrafallopian transfer generated pregnancies. The outcomes of the pregnancies with respect to abortion, ectopic gestation, and multiple gestation were evaluated independently by method and by center. Only with multiple gestation by center was a difference seen. Variables examined included estradiol levels, luteal phase support, maternal age, and prior reproductive history, and the number of eggs or embryos replaced.

Highly purified human-derived follicle-stimulating hormone (Bravelle®) has equivalent efficacy to follitropin-beta (Follistim ®) in infertile women undergoing in vitro fertilization

BackgroundThese data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle(R)) and recombinant follitropin-β (Follistim(R)) in women undergoing in vitro fertilization.MethodsThis report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle(R) (n = 120) or Follistim(R) (n = 118), followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary.ResultsSimilar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle(R) consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05). The overall incidence of adverse events was similar in both groups, but compared to Follistim(R), injections of Bravelle(R) were reported by patients to be significantly less painful (P < 0.001).ConclusionsBravelle(R) and Follistim(R) had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle(R) injections were reported to be significantly less painful.

Genetic offspring in patients with vaginal agenesis: Specific medical and legal issues

OBJECTIVE There are new options for genetic offspring in patients with vaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome). The reported world experience to date with genetic offspring of patients with vaginal agenesis consists of five pregnancies (including two reported here and two frozen embryos). The specifics of these cases are presented for discussion. STUDY DESIGN We present a retrospective description of two women with vaginal agenesis and their matched gestational carriers with positive outcome of two live births. Care was delivered in a private in vitro fertilization and gamete intrafallopian transfer program. RESULTS In vitro fertilization of oocytes gathered from the genetic mother with vaginal agenesis and sperm from the genetic father were transferred to a gestational carrier. Two live births and one blighted ovum pregnancy resulted. CONCLUSION Until recently, treatment for patients with vaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) has centered on the creation of a functional vagina. The technology of in vitro fertilization and embryo transfer, allowing for collection of oocytes from the genetic mother, fertilization by the genetic father, and placement into a gestational carrier, enables a woman without a uterus to have her own genetic children. The specific medical and legal issues involved in facilitating genetic offspring in these instances must be considered; these include the initial matching of the genetic parents with the gestational carrier, cycle synchronization for in vitro fertilization and embryo transfer, anatomic difficulties of oocyte retrieval, birth certificate documentation, and the current legal status of a gestational carrier.

Predicting success of gamete intrafallopian transfer.

OBJECTIVES To examine seminal parameters predictive for success in a cycle of GIFT and to construct an algorithm using pertinent seminal data as well as easily obtained historical data to predict pregnancy and viable pregnancy rates. DESIGN A retrospective study of 544 cycles in 376 couples. SETTING A private IVF-ET and GIFT center. PATIENTS Couples in a GIFT program with a mean of 53.6 months of infertility who had failed to conceive with other therapies. INTERVENTIONS Gamete intrafallopian transfer. MAIN OUTCOME MEASURES Pregnancy as a function of laboratory historical data with emphasis on seminal parameters. RESULTS Motility was the only seminal parameter that was predictive. Success was correlated with the number of oocytes returned and inversely related to female age. An algorithm to predict pregnancy in a GIFT cycle as well as viable pregnancy was constructed. CONCLUSIONS Motility is the only seminal parameter predictive for success in a GIFT cycle. An easily programmable algorithm can be constructed to help patient and physician decide on the appropriateness of GIFT for each couple.

Leuprolide acetate-prepared in vitro fertilization-gamete intrafallopian transfer cycles: efficacy versus controls and cost analysis *

OBJECTIVE To evaluate the effect of gonadotropin-releasing hormone agonist (GnRH-a) when given through stimulation with gonadotropins versus stopping it as stimulation was initiated versus a control group unprepared in this manner. Also, to construct a cost analysis for this type of therapy in an in vitro fertilization-gamete intrafallopian transfer program (IVF-GIFT). DESIGN Prospective, consecutive, randomized, with a control group. SETTING An out-patient IVF-GIFT program. PATIENTS One hundred new patients entering an IVF-GIFT program. INTERVENTIONS In vitro fertilization or GIFT cycles with or without preparation (pituitary suppression) by GnRH-a administration in which suppression was continued or halted as gonadotropins were begun. MAIN OUTCOME MEASURES Cancellation rates, ampules, and days of gonadotropin use, costs, estradiol (E2) level, egg numbers and quality, and pregnancy rates. RESULTS Stopping GnRH-a (leuprolide acetate) therapy as stimulation was begun did not lessen the suppressive effect in reduction of spontaneous luteinizing hormone surge as seen with continued use of agonist. In contrast, the control group had a 30.3% cancellation rate before ovum retrieval. The E2 and egg data among the groups were similar, but as expected, agonist use led to the need for more and longer duration of gonadotropin stimulation. Pregnancy rates were not different by group. Costs were approximately even by the third initiated cycle.

Subcutaneously administered repronex in female patients undergoing in vitro fertilization is as effective and well tolerated as intramuscular menotropin treatment1

Abstract Objective: To determine the efficacy and safety of Repronex SC as compared with Repronex IM and Pergonal IM in patients undergoing IVF. Design: Open-label, randomized, parallel-group, multicenter study. Setting: Fifteen academic and private fertility clinics with IVF experience. Patient(s): Premenopausal women with regular ovulatory menstrual cycles undergoing IVF for infertility attributable to tubal factors, endometriosis (stage I or II), or unknown factors. Intervention(s): Down-regulation with leuprolide acetate followed by up to 12 days of treatments with gonadotropins, hCG administration, oocyte retrieval, and embryo transplant. Main Outcome Measure(s): Mean number of oocytes retrieved, chemical, clinical, and continuing pregnancies, incidence of oocyte retrieval and embryo transfer, and peak serum E 2 concentrations. Result(s): There were no significant differences among the treatment groups except for a higher percentage of continuing pregnancies in the Repronex SC group. Gonadotropin therapy was well tolerated in all three treatment groups. The Repronex SC group had a significantly higher incidence of transient mild/moderate injection site reactions during the first few days of therapy. Conclusion(s): Repronex SC is comparable in therapeutic effectiveness and safety to Repronex IM and Pergonal IM in patients undergoing IVF and provides an alternative route of injection for self-administration of gonadotropin.

Insemination data on men with varicoceles

Objective To determine possible benefits of sperm processing and intrauterine insemination (IUI) for a group of men with a varicocele history who had not achieved a pregnancy by natural coitus (mean duration of infertility 42.2months). Design A retrospective study including infertile men with varicoceles who were classified by their semen analyses and sperm penetration assays (SPAs). Setting Private practice of infertility. Patients Seventy-one infertile couples. The husbands had a varicocele history and were grouped into four clinical categories (14 untreated, 5 medical treatment, 34 varicocelectomies, and 18 varicocelectomies plus medical treatment). The wives were studied or treated before IUI. Interventions Varicocelectomies were performed on the males when indicated. Female studies included laparoscopies as indicated intrauterine insemination with Tomcat catheter (Sherwood Medical, St. Louis, MO) was performed in all cases. Main Outcome Measures Overall pregnancy rates (PRs) and fecundity rates with sperm processing and IUI. Results Six pregnancies occurred with 66cycles of sperm processing and IUI among 28 men with normal SPAs (PR 21%, fecundity rate=0.09). In contrast, there were no pregnancies with 121cycles among 43 varicocele patients with abnormal SPA results or with low values for all three semen parameters. Conclusions Sperm processing and IUI may be beneficial for selected patients with varicoceles who had not achieved a pregnancy by coitus.

Antibodies to Phospholipids and Nuclear Antigens in Patients with Repeated Abortions

The frequency of positive tests for antibodies to nuclear antigens (antinuclear, deoxyribonucleic acid, Ro, La, Smith, and ribonucleoprotein) or to phospholipids was investigated in 82 patients with isolated repeated abortions. Patients with a positive antibody test (positive or negative deoxyribonucleic acid antibodies) appeared to be a separate subgroup of those with unexplained repeated abortions from those with antibodies to cardiolipin. A total of 13.1% of the 61 patients with unexplained repeated abortions had elevated levels of IgM and/or IgG anticardiolipin antibody, while none were found in patients with explained abortions (p less than 0.1). Enzyme-linked immunosorbent assays for antibodies binding to other phospholipids suggested that sera from patients with repeated abortions who had the lupus anticoagulant contained antibodies that were most often of the IgG class with affinity for negatively charged phospholipids. Binding of IgG but not IgM antibodies to cardiolipin correlated closely with that to other negatively charged phospholipids. The use of clotting tests for the lupus anticoagulant to screen patients with repeated abortions for associated autoantibodies is likely to significantly underestimate the extent of this clinical problem.