Zygote intrafallopian transfer as a treatment for nontubal infertility: a 2-year study.

Zygote intrafallopian transfer (ZIFT) was used as a treatment for long-standing nontubal infertility for a 2-year period. The overall clinical pregnancy rate for 114 tubal transfers was 40.4% with a delivery/ongoing rate of 34.2%. Concurrent use of in vitro fertilization and embryo transfer (IVF-ET) for tubal factor infertility gave significantly lower clinical pregnancy and delivery/ongoing rates (21.1% and 15.8%, respectively). The use of gamete intrafallopian transfer (GIFT) for nontubal infertility yielded a 32% clinical pregnancy rate and a 26% delivery rate for 53 transfers. Zygote intrafallopian transfer resulted in an implantation rate per zygote of 17% overall compared with 8.1% per embryo for IVF-ET and 11.2% per oocyte for GIFT. The transfer of three zygotes per patient gave the same clinical pregnancy rate as the transfer of four while reducing the incidence of multiple gestation from 19% to 7.8% per transfer. No significant decline in the clinical pregnancy or delivery rate was seen with ZIFT in women aged 25 through 39.

Zygote intrafallopian transfer with "donor rescue": a new option for severe male factor infertility.

Clinical pregnancies have been initiated by ZIFT using zygotes produced by reinsemination of oocytes with donor sperm ("donor rescue") after an initial 15- to 20-hour exposure to husband's sperm. A total of 54 oocytes from four couples experiencing failed fertilization by husband's sperm were reinseminated with donor sperm, resulting in 38 zygotes (70.4% fertilization). Four zygotes were transferred during ZIFT in each case and resulted in two (50%) continuing pregnancies. Additional zygotes from donor reinsemination were cryopreserved for each couple. Donor rescue expands the utility of ZIFT as a treatment for male factor infertility.

Inhibition of luteinizing hormone/human chorionic gonadotropin-stimulable adenylyl cyclase activity in rat luteal membranes by nonsteroidal component(s) in human follicular fluid.

We examined the ability of nonsteroidal components of human follicular fluid (hFF) to alter gonadotropin responsiveness using the LH/hCG-sensitive adenylyl cyclase system of rat luteal membranes. Follicular aspirates were obtained from regularly ovulatory women (n = 10) whose follicles were stimulated by human menopausal gonadotropin and hCG as part of an in vitro fertilization program. hFF from large follicles was pooled and extracted with 10% (wt/vol) activated charcoal. Maximal hCG stimulation of adenylyl cyclase activity obtained with 10 micrograms/ml hCG and 100 microM of the hydrolysis-resistant GTP analog guanyl 5'-yl-imidodiphosphate was significantly inhibited by hFF in a dose-dependent manner. Addition of about 500 micrograms hFF protein caused inhibition of 70% compared to the control value. Fractionations of hFF by ultrafiltration using membranes of precalibrated pore size demonstrated that the inhibitory activity was associated with a less than 10,000 mol wt fraction; 3 micrograms protein/assay of this fraction resulted in 50% inhibition (IC50) of maximal hCG stimulation. The inhibitory activity also passed through an Amicon YM-2 membrane (mol wt retention, 1,000), but not through an Amicon YC-05 membrane (mol wt retention, 500). An IC50 of about 0.01 microgram protein/assay was found for both the 500-1,000 and the 1,000-5,000 mol wt fractions. NaF or forskolin-stimulated adenylyl cyclase activity was not altered by unfractionated hFF or by the 500-10,000 mol wt subfractions, suggesting that inhibition was limited to LH/hCG stimulation. Further analysis of the effects of low mol wt fraction on hCG stimulation of adenylyl cyclase indicated that enzyme inhibition was not accompanied by a shift in the hCG concentration required for half-maximal stimulation (the apparent activation constant) compared to dose-response curves obtained in the absence of added fraction. Equilibrium binding studies showed that [125I]hCG interaction with luteal membranes was significantly inhibited by hFF; 7 micrograms protein/assay of the less than 10,000 mol wt fraction reduced specific binding by 60%. Moreover, kinetic analysis carried out in the absence or presence of a fixed amount of low mol wt fractions revealed a competitive type of binding inhibition. Our data demonstrate that a nonsteroidal component(s) of hFF has a direct inhibitory effect on LH/hCG-responsive luteal adenylyl cyclase and that the inhibitor(s) exerts its actions through a mechanism involving competition with LH/hCG for the same binding sites.

Gamete intrafallopian transfer (GIFT): use of minilaparotomy and an individualized regimen of induction of follicular development.

The performance of the gamete intrafallopian transfer (GIFT) technique, utilizing an individualized regimen of follicular induction and minilaparotomy in 45 patients with infertility of varying etiologies is reported. The induction regimen consisted of the administration of clomiphene citrate, 100 mg, from day 3 to day 7, and 150 IU FSH/LH (human menopausal gonadotropin [hMG]) from day 6 on. Human chorionic gonadotropin (hCG; 10,000 IU) was administered when at least two follicles measured 16 mm or more in diameter and when serum estradiol (E2) measurement revealed levels of 350 pg/ml per each main follicle. Up to two oocytes and 100,000 motile sperm were transferred to the fallopian tubes via the fimbria, using a catheter. Of the 45 cases, 13 became pregnant by clinical criteria (29 per cent). Of these 13 pregnancies, nine continued to term (69 per cent), three miscarried spontaneously (12 per cent) and one was an ectopic (7 per cent). Of the nine pregnancies that continued to term, five (55 per cent) were twins. Details of the GIFT procedure as well the preliminary non-human primate research studies that led to the development of the GIFT technique are discussed. It is concluded that GIFT is an excellent alternative to in vitro fertilization and embryo transfer (IVF; ET) in all cases of infertility that failed to conceive using conventional forms of therapy and in which the female partner presents at least one normal fallopian tube.

Preliminary experiences with gamete intrafallopian transfer (GIFT).

This article describes the first series of patients to undergo gamete intrafallopian transfer (GIFT) as a treatment for infertility. Ten patients with the diagnosis of either unexplained infertility or male factor were treated with human menopausal gonadotropin and human chorionic gonadotropin before surgery by laparoscopy or minilaparotomy. Semen was collected 2.5 hours before oocyte pickup at surgery and treated by the technique of wash and swim-up. After gamete evaluation, one or two oocytes and 100,000 actively motile sperm were loaded into a catheter and introduced through the fimbria. The contents of the catheter were gently emptied at a site approximately 1.5 cm inside each fallopian tube. Patients received progesterone in oil, 12.5 mg/day, from day 4 after GIFT until up to 8 weeks of gestation. Four patients became pregnant: two pregnancies aborted; the other two pregnancies proceeded to the delivery of viable infants. GIFT may be considered as an alternative to in vitro fertilization in infertility cases in which at least one fallopian tube is patent.

Psychosocial and psychophysiologic aspects of reproduction: the need for improved study design.

PIP: This essay delineates several of the more ctirical design issues involved in psychosocial research in the reproductive field: prospective design; control groups, blinded designs, placebos; crossover design; multivariate statistical analysis; sample size and significance; low attrition rates/refusal rates; and long periods of follow-up. Examples are drawn primarily from the areas of infertility and sterilization. The dual goal in infertility research in general is to understand the mechanisms involved in reproduction and to determine which treatment modalities are most effective in alleviating impaired reproduction. It is important to determine the contribution and interplay of psychological factors in this regard. A major purpose of psychosocial research in the field of sterilization is to identify any physical or psychosocial sequelae of procedures that terminate fertility. This type of information is useful in providing future sterilization candidates with complete information to facilitate informed decisions and helping to identify women who may be at high risk of regret so that appropriate counseling may be provided preoperatively. In most instances, studies of infertility employ prospective designs, but studies of psychologic factors in this area tend to describe experience retrospectively. Usually, without benefit of a trial, they advocate counseling services, group therapy, or psychiatric intervention. As for sterilization studies, a common practice is to ask subjects at varying postsurgical intervals to compare their preoperative and postoperative status on various outcome variables. This retrospective approach is problematic because there may be a tendency for respondents to reevaluate prior experience in the light of recent events. Without the use of appropriate control or comparison groups, it is impossible to determine if changes resulted from a given procedure or were due to other factors, including chance. Use of a placebo group helps determine whether observations are related to the experimental therapy or are associated nonspecifically with intervention. This concern may be particularly important when psychologic effects are studied. The use of placebo treatment is not applicable to studies of sterilization effects and would be unethical. It is essential to use multivariate statistical analysis as opposed to only chi-square and t-tests to determine which factors are both significantly and independently associated with outcome variables.^ieng

Human chorionic gonadotropin and steroid concentrations in human follicular fluid in relation to follicle size and oocyte maturity in stimulated ovarian cycles.

The concentrations in follicular fluid (FF) of beta hCG, progesterone (P), estradiol (E2), androstenedione (A) and testosterone (T) by RIA were determined, in order to study the follicular micro-environment in stimulated cycles. Patients received either clomiphene with hMG plus hCG or hMG plus hCG. With increasing volume of FF (obtained at laparoscopy), P significantly increased (p less than 0.04) and hCG (p less than 0.0004) and T (p less than 0.05) significantly decreased with a borderline decrease in A (p less than 0.07). Progesterone also increased with advancing oocyte maturity. Beta-hCG and P were positively correlated with E2 and negatively correlated with A levels. It is suggested that FF hCG and progesterone levels may be markers of follicular development in stimulated cycles.

Ovarian function after radical hysterectomy for stage IB carcinoma of cervix.

Ovarian function was assessed in 20 patients after radical hysterectomy and lymph node dissection for Stage IB cervical carcinoma. All patients were under 45 years of age, and four were or had been on estrogen therapy for postmenopausal symptoms. The other 16 patients were free of symptoms and demonstrated premenopausal gonadotropin profiles. Fourteen of these 16 had luteal phase serum progesterone levels. Only one patient required reoperation for a pathologic condition of the adnexa. A surgical approach to Stage IB cervical carcinoma conserves ovarian function in 80% of patients.