Assisted reproductive technology: the state of the ART.

At least one in ten couples of reproductive age is affected by infertility. Tubal disease, ovulatory defects, endometrosis and abnormal sperm physiology are the most common causes of failure to conceive. Many of these disorders can be treated successfully with surgery, ovulation induction or intrauterine insemination, but in selected cases, or where there is long-standing intractable infertility, assisted reproductive technology (ART) becomes the treatment of choice. We provide an overview of the techniques for assisted reproduction, including in vitro fertilization, gamete intrafallopian transfer and other related procedures. Indications for treatment, patient evaluation and advances in reproductive technology including embryo cryopreservation, micromanipulation and donor gametes are also reviewed.

Modern medical management of endometriosis.

The modern medical management of endometriosis has changed considerably since the first attempts were made to control this disease hormonally over four decades ago. Currently, there are multiple choices for the clinician and patient, including oral contraceptives, danazol, GnRH agonist analogues, and gestrinone. Several advances have been made in the use of GnRH agonists in preventing some of the untoward effects of prolonged hypoestrogenism. These add-back regimens provide the best therapy available today for prolonged medical control of endometriotic symptoms. The antiprogesterones (RU-486) hold promise for the future, but are still in the investigational stage of development.

Ovulation induction in the estrogenized anovulatory patient.

Ovulation induction is one of the greatest success stories in reproductive endocrinology. With appropriate therapy in properly f1p4cted patients, the conception and live birth-rates in treated patients are almost indistinguishable from normal. In the estrogenized woman there are many different techniques to reverse the condition of chronic anovulation. With clomiphene citrate, up to 80% of patients will ovulate, and approximately half will conceive. In women who fail clomiphene therapy, injectable gonadotropins are usually successful in inducing ovulation. New protocols for administering these powerful agents have minimized the risk of ovarian hyperstimulation and multiple pregnancy. When medical therapy fails to result in successful ovulatory cycles, surgical treatments can be considered. Laparoscopic ovarian ablation has been shown to be effective treatment. Whether this less invasive surgery results in fewer adhesions than conventional ovarian wedge resection remains to be proven. By carefully considering each patient and individualizing treatment based on a full knowledge of alternatives, ovulation induction remains one of the most challenging and rewarding treatments in reproductive endocrinology.

Transient hyperprolactinemia during cycle stimulation and its influence on oocyte retrieval and fertilization rates.

Prolactin (PRL) has been shown to have inhibitory effect on follicle-stimulating hormone induced aromatase activity and estrogen biosynthesis in human granulosa cells cultured in vitro. To investigate the validity of the hypothesis that transient hyperprolactinemia during controlled ovarian hyperstimulation might influence follicular steroidogenesis and oocyte maturation, we measured serum PRL, estradiol, and progesterone before aspiration of oocytes in women undergoing ovarian stimulation (n = 108) in in vitro fertilization-embryo transfer. No correlation was detected between PRL and total number oocytes, number mature oocytes, fertilization rate, cleavage rate, and pregnancy rate. Transient elevation of PRL was a common finding in patients (57%) but was not associated with a poor clinical outcome.

Suppression of LH-stimulated prostaglandin and progesterone accumulation in rat granulosa cells by isoquinolinesulfonamide protein kinase inhibitors.

Rat granulosa cells were incubated with isoquinolinesulfonamide inhibitors of protein kinases A and C and/or LH, dibutyryl cAMP (dbcAMP), tetradecanoylphorbol acetate (TPA), cholera toxin, or forskolin for 5 h. H7 (25 microM) was observed to inhibit LH, cholera toxin or dbcAMP stimulation of prostaglandin (PGE), and progesterone accumulation. H7 produced inhibition when added as little as 2 min before and as long as 1 h after LH. HA1004 was ineffective against LH or cholera toxin stimulation of PGE or progesterone at up to 100 microM. H9 blocked some LH and forskolin responses at 25 microM, but required a 50 microM concentration to minimally affect TPA stimulation. Cytotoxicity was not observed at the concentrations and times of isoquinolinesulfonamides tested. H7 and H9, therefore, suppress LH stimulation of granulosa cell functions in a dose- and time-dependent manner consistent with inhibition of protein kinases A and/or C, and consonant with a requirement for such kinases in LH action.

Current management of a donor insemination program.

Substantial evidence now exists to show that considerable maternal-fetal morbidity may result from microbiologic transmitted diseases that can be transmitted through artificial insemination by donor. In the present decade it has become increasingly clear that the use of fresh semen is potentially hazardous and its use has been discouraged by both the CDC and AFS. To minimize this risk, donor insemination programs should establish their own guidelines to thoroughly evaluate potential semen donors via history, physical examination, and laboratory evaluation before the use of donor semen after cryopreservation and quarantine. The management of a donor insemination program in the future requires uniform procedures for rigorous genetic and microbiologic screening before the selection and use of semen donors for artificial insemination.