Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. I. Effects of varying duration of estradiol administration.

This study was designed to investigate the effects of increased serum concentrations of estradiol of varying durations upon the gonadotropin responses to synthetic gonadotropin-releasing hormone (GnRH or LRF). Beginning at 8:00 PM on the first day of the menstrual cycle, subjects received im injections of estradiol benzoate (E2B), 5 mug/kg initially, followed by 2.5 mug/kg every 12 h for a total of 3, 5, 7, 9, or 11 injections. Twelve h after the last E2B injection, or 36, 60, 84, 108, or 132 h after the first injection of E2B (2 subjects at each time interval), each subject received 100 mug GnRH, iv. In addition, each subject received 100 mug GnRH iv during one of the seven days of the antecedent (control) menstrual cycle during which no exogenous estradiol was administered. When GnRH was infused 36 h after the initiation of E2B pretreatment, there was no significant LH or FSH increase. In contrast, LH and FSH responses were augmented and prolonged when compared with control cycles when GnRH was administered at 84, 108, or 132 h. At 60 h, responses of LH were augmented, although not to as great a degree. FSH responses were not augmented at 60 h. Expressed as maximal increase from baseline, gonadotropin responses following E2B were 1 1/2 to 9 times those achieved during control cycles (without E2B). Since mean serum estradiol concentrations at 36 h (185.9 +/- 20.0), when gonadotropin responses were absent, were similar to those at 60 (157.7 +/- 31.6), 84 (186.2 +/- 38.1), 108 (181.3 +/- 46.7), and 132 h (128.0 +/- 43.0 pg/ml), when responses were augmented, these results support the concept that the modulating effect of estradiol on pituitary response is dependent upon the duration of exposure of the hypothalamic-pituitary system to increased concentrations of estradiol. It is probable that the duration of the late follicular phase rise in serum estradiol is responsible, at least in part, for the augmented gonadotropin response seen at midcycle.

Changing patterns of FSH and LH response to gonadotropin-releasing hormone in the puerperium.

Gonadotropin responses to synthetic gonadotropin-releasing hormone (GnRH or LRF), as well as basal concentrations of gonadogropins, estradiol, and prolactin, were determined at weekly intervals during the first eight weeks post partum in seven non-nursing, non-steroid-treated women. The results were compared with those of a group of eleven women studied on the second day of the menstrual cycle. In the postpartum group, baseline concentrations of LH and FSH similar to those seen in the early follicular phase of the menstrual cycle occurred by the third week post partum. In response to an iv bolus of 100 mug GnRH, elevations of serum LH: 1) occurred as early as the second postpartum week; 2) were less than those of women during the early follicular phase until the fourth postpartum week; and 3) were exaggerated (when compared with those ob subjects in the early follicular phase) during the fifth through the eighth week post partum. Similarly, the FSH responses to GnRH in the puerperium were similar to those of the subjects during the early follicular phase by the third week post partum, and were exaggerated during the second month post partum. These studies demonstrate that human pregnancy is followed by a period of relative pituitary refractoriness followed by one of increased responsiveness to GnRH.

Modulation of pituitary gonadotropin response to gonadotropin-releasing hormone by estradiol.

PIP: The effects of 17beta-estradiol on the responsiveness of the pituitary to gonadotropin-releasing hormone (GnRH) and on the rate of disappearance of GnRH were studied in 15 healthy nulliparous women aged 18-21 years. The women were divided into 3 groups: Group 1 received no estradiol, Group 2 received the amount of estradiol needed to achieve a circulating level comparable with that in the late follicular phase, and Group 3 received enough estradiol to achieve a concentration similar to that at midcycle. Following administration of GnRH, a marked increase in both LH and FSH was seen in Group 1 subjects. A smaller increase in LH level was observed in Group 2, and virtually no LH response occurred in Group 3. There was no significant increase in FSH level in either group treated with estradiol. The infusion of estradiol did not affect the maximal plasma concentration of exogenously administered GnRH or its disappearance rate in 4 women studied.^ieng

Photocoagulation of endometriosis by the argon laser through the laparoscope.

Photocoagulation of peritoneal implants of endometriosis was performed in five women during laparoscopy to evaluate infertility. A 600-microns flexible quartz fiber was passed into the abdomen through a suprapubic incision using an instrument with a steerable operating tip. Thirty-one implants of the uterosacral ligaments, ovaries, fallopian tubes, bladder, and sigmoid were photocoagulated without complication or perforation. Because of the selective absorption of the argon laser by the hemoglobin of the endometriosis implants and the ease of photocoagulating implants at laparoscopy, this technique may eventually be an important therapeutic modality for the treatment of endometriosis.

Medical and psychologic characteristics of women presenting with premenstrual symptoms.

To establish the necessary elements of a program of evaluation and treatment of premenstrual syndrome, the medical and psychologic characteristics of 68 consecutive women presenting because of premenstrual symptoms were determined and compared with those of a similar group of 34 women without premenstrual symptoms (control group). Women with premenstrual symptoms exhibited a significantly greater frequency of previously undetected medical, psychologic, and marital problems than did controls. These findings demonstrate the need for a multidisciplinary comprehensive program of evaluation and treatment of the medical, psychologic, and mental health of women who present because of moderate-to-severe premenstrual symptoms.

Müllerian agenesis, hypoplasia of distal extremities, unusual dermatoglyphics, and pigmentation.

The case of a 17-year-old girl with müllerian agenesis, hypoplasia of the distal extremities, unusual dermatoglyphic findings, and mottled skin pigmentation is reported. The family history indicates that the maternal grandmother's sisters were similarly affected with müllerian agenesis, suggesting a dominant gene with variable penetrance in this family.

Fetoscopic neodymium:YAG laser occlusion of placental vessels in severe twin-twin transfusion syndrome.

Most pregnancies with severe twin-twin transfusion syndrome before 27 weeks' gestation result in perinatal death. Previous attempts at therapy have been generally unsatisfactory and rarely successful. We have developed a technique for intrauterine ablation of the vascular communications between the fetoplacental circulations with a fetoscopically directed neodymium:YAG laser. The operation was performed on three women at risk for pregnancy loss from acute hydramnios at 18.5, 22, and 22.5 weeks' gestation. The first two procedures were uneventful, but the third was complicated by a placental vessel perforation. The first two patients delivered at 27 and 34 weeks after premature rupture of membranes and spontaneous labor, whereas the third woman developed severe preeclampsia at 29 weeks which necessitated delivery. Four of the six infants survived. Clinical and ultrasonographic evidence, as well as pathologic examination of the placentas, suggested that stabilization or resolution of the syndrome was due to photocoagulation of the vascular communications. This initial experience suggests that fetoscopic laser occlusion of placental vessels is feasible and superior to previous therapies because it treats the underlying pathophysiology directly.

Amenorrhea, hyperprolactinemia and pituitary enlargement secondary to primary hypothyroidism. Successful treatment with thyroid replacement.

A 22-year-old nulliparous woman presented with primary amenorrhea, primary hypothyroidism, hyperprolactinemia, and radiologic evidence of pituitary enlargement. Investigation demonstrated limited reserves of ACTH and growth hormone. Circulating concentrations of TSH and prolactin were elevated; they increased in response to thyrotropin releasing hormone and decreased following L-dopa administration. After treatment with L-tri-iodothyronine, serum TSH and prolactin levels fell markedly, reserves of growth hormone and ACTH returned to normal, menstrual periods began, and the patient conceived. She experienced an uncomplicated prenatal, intrapartum, and postpartum course. It is thought that this patient represents a distinct clinical entity: a syndrome of amenorrhea, hyperprolactinemia, and pituitary enlargement, all secondary to primary thyroid failure. This syndrome should be distinguished from the Forbes-Albright syndrome, as it is reversible with thyroid replacement therapy. Recognition of this syndrome may thus spare the patient unnecessary, and potentially dangerous, pituitary surgery or irradiation.

The use of the argon laser in the treatment of experimental endometriosis.

The argon laser offers several theoretical advantages over excision, electrocautery, or CO2 laser therapy for the treatment of peritoneal implants of endometriosis. Therefore, a study of the feasibility of the argon laser for the treatment of endometriosis was performed using five virgin New Zealand White rabbits. Following 6 days of estrogen administration, each animal underwent laparotomy with excision of the right uterine horn. Sections of endometrium were sutured to several peritoneal surfaces. Approximately 3 weeks later the endometrial implants were photocoagulated with the argon laser (488 nm, 2 W, 2-mm spot size, 3 to 5 seconds). Histologic examination of the sites of laser therapy demonstrated complete ablation of the endometriosis with 0.25-mm damage to the underlying tissue and surrounding tissue.

Argon laser therapy of endometriosis: a review of 92 consecutive patients.

The conception rate, relief of pain, and safety of argon laser photocoagulation of endometriosis were evaluated in 92 patients. All patients were treated at the time of diagnosis with the argon laser delivered through a flexible quartz fiber passed through the operating channel of a standard and unmodified laparoscope. The uncorrected pregnancy rate was 34% (19 of 56), with 64% of the pregnancies occurring within 6 months of therapy. The conception rate was slightly greater in women with infertility of 24 months or less and in women without other fertility factors. Ninety-two percent of 50 women with pelvic pain reported a reduction of their pain after treatment. The argon laser is an effective, simple, and safe alternative for the treatment of mild or moderate endometriosis.

Subcutaneously administered Repronex in female patients undergoing in vitro fertilization is as effective and well tolerated as intramuscular menotropin treatment. Repronex SC, IVF Study Group.

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 E2 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.

Microsurgical ovarian transplantation in the primate.

We have developed a technique for orthotopic transplantation of ovaries by microsurgical reanastomosis of the ovarian blood vessels in rhesus monkeys. Four monkeys receiving autografts resumed cyclic menses and had postoperative circulating luteinizing hormone (LH) and progesterone concentrations consistent with developing follicles and corpus luteum function. Postoperative luteal phase ovarian biopsies were indicative of ovulation in three of the four animals. However, in a fifth recipient an ovarian allograft from an unrelated donor was rejected despite the use of a standard immunosuppressive regimen. This study suggests that ovarian transplantation by direct vascular anastomosis is a technically feasible surgical procedure in the human, where the vascular anatomy is similar and the caliber of the ovarian vessels if greater than in the rhesus monkey.

Pseudomyxoma peritonei associated with secondary infertility.

In summary, we report a case of secondary infertility attributed to pseudomyxoma peritonei caused by ruptured appendiceal mucocele. Resection of the tumor and visible mucinous ascites resulted in spontaneous conception. We hypothesize secondary infertility was caused by significant peritoneal inflammation and inhibition of sperm-oocyte interaction from the ascites.

Are we exploiting the infertile couple?

We hope that this article brings into focus some problems that merit consideration and debate. These thoughts come from a group of individuals who are actively engaged in reproductive endocrine/infertility practices with special interests ranging from ovulation induction to IVF to laser surgery. As a group, we practice in all parts of the country, and the problems mentioned are not restricted to any individual or region. We urge that all of us be candid with ourselves and our colleagues about what we can and cannot do for the infertile couple. We suggest that gynecologists ask themselves this question and proceed when the answer is affirmative: "Is this procedure really in the patient's best interest?"

Hypothalamic gonadotropin releasing hormone: physiologic and clinical considerations.

Despite the efforts of a large number of investigators, the role of GnRH in clinical gynecology is uncertain. At present, its greatest utility is in research directed toward the understanding of hypothalamic-pituitary interrelationships. However, a clear understanding of the hypothalamic control of gonadotropin secretion awaits the actual measurement of the secretion of GnRH by the hypothalamus. In addition, a better understanding of the ability of the pituitary to secrete gonadotropins in various disorders of menstruation and maturation will probably be achieved through the determination of the capacity of the pituitary to synthesize as well as release gonadotropins in response to GnRH. Such determinations will probably utilize repeated or continuous infusions of GnRH rather than the currently more popular single injection technique. Finally, GnRH may be useful in the induction of ovulation. A definition of its role in ovulation induction awaits the results of additional clinical studies. Understanding of the nature of hypothalamic control of the pituitary is as yet incomplete. The availability of hypothalamic releasing factors will make it possible to study in greater detail the mechanisms by which the fine regulation of the endocrine system is achieved.

Firstborn adolescent daughters and mothers with and without premenstrual syndrome: a comparison.

Firstborn adolescent daughters and their mothers with and without premenstrual syndrome (PMS) were evaluated for two menstrual cycles in order to compare menstrual, postmenstrual (follicular), and premenstrual (luteal) symptomatology. Physical and psychological symptoms were evaluated according to the Premenstrual Assessment Form (PAF) and the Utah PMS Calendar II. The onset of the luteal phase was defined as the day of the midcycle surge of luteinizing hormone (LH), determined by utilizing the CUE Ovulation Predictor. The PAF showed that 1) irrespective of diagnosis, severity of symptoms was not significantly different between adolescents and adults; however, 2) when daughters and mothers were grouped according to mother's diagnosis, the PMS mother/daughter dyads experienced significantly more premenstrual symptoms when compared to the non-PMS mother/daughter dyads. Furthermore, the PMS Calendar revealed menstrual cycle phase delineation. There were no significant differences in severity of symptoms between adults and adolescents during the postmenstrual (follicular) phase and the premenstrual (luteal) phase. However, the adolescents experienced significantly more symptoms during the menstrual phase than the adults. 1) There were no significant differences in severity of adolescents' menstrual symptoms and their premenstrual (luteal) symptoms; 2) the number and severity of luteal phase symptoms were significantly greater for the women with PMS and their daughters than women without PMS and their daughters.

KTP and argon laser laparoscopy.

Although it is true that the clinical results of surgery performed with lasers through the laparoscope are no better than those achieved with laparotomy, the laser has had a significant impact on the treatment of pelvic abnormalities in infertile women. The most notable contribution of lasers has been to extend the ability of the reproductive surgeon to perform laparoscopic surgery. As a result, many patients have been spared the added expense, pain, and hospitalization associated with a laparotomy. The argon and KTP lasers provide an option for the operative laparoscopist who is looking for a user-friendly system. The simplicity of these systems is especially appealing to the beginning or occasional laser laparoscopist. Even the experienced and expert operative laparoscopist, however, will find these lasers to be an important addition to their surgical armamentarium.

Laparoscopic treatment of endometriosis.

Advances in operative laparoscopy have been useful in the treatment of pelvic endometriosis. While these advances have not yet led to improved pregnancy rates, they have decreased the cost and morbidity of surgery for endometriosis.

Premenstrual syndrome. Seven steps in management.

Many forms of therapy for premenstrual syndrome (PMS) are available, but appropriate therapy involves more than a pill, more than changing attitudes, and more than removing stress. Even with treatment, the problems that preceded the PMS may persist and those that have been created by it may be slow to resolve. However, most patients experience significant improvement in their sense of well-being and quality of life with appropriate, multidisciplinary therapy.

Premenstrual symptoms: evaluation and treatment.

Critics who claim there is no therapy for PMS should now recognize that there are many ways to treat this condition. Appropriate therapy for PMS is more than a pill, more than changing attitudes, more than removing stress from one's life. Indeed, therapy for PMS is not always easy, for the problems that preceded the PMS may persist and the problems created by the PMS may be slow to heal. However, the good news is that most women with PMS will experience significant improvement in their sense of well-being and their quality of life with appropriate and multidisciplinary therapy.