J. R. T. Coutts

Successful treatment of infertile women with oligomenorrhoea using a combination of an LHRH agonist and exogenous gonadotrophins

Summary. Eight oligomenorrhoeic patients with increased luteinizing hormone (LH) and androgen levels who had failed to conceive during prolonged anti‐oestrogen therapy received a new treatment. Large doses of an LH‐releasing hormone (LHRH) analogue (HOE 766) were used to suppress circulating gonadotrophin concentrations and block the positive feedback gonadotrophin surge. Ovulation was induced during continued LHRH analogue treatment with exogenous gonadotrophins without interference from the patients own pituitary. Seven of eight patients conceived rapidly without premature luteinization and without excessive ovarian enlargement. These complications had occurred in control treatment cycles using exogenous gonadotrophins in the absence of the LHRH analogue.

Luteinization to oocyte retrieval delay in women in whom multiple follicular growth was induced as part of an in vitro fertilization/gamete intrafallopian transfer program

Different luteinization-to-oocyte-retrieval delays were examined in 64 IVF/GIFT patients. Multiple follicular stimulation was induced with combined therapy of hMG and GnRH-a to create continuous pituitary suppression and thus eliminate endogenous gonadotropin fluctuations. The results demonstrated that with this induction regime, the time interval can be extended to 39 hours without preoperative ovulation and with improved oocyte maturity.

Combined gonadotropin-releasing hormone analog and exogenous gonadotropins for ovulation induction in infertile women: Efficacy related to ovarian function assessment

The ovarian function of infertile women with normal menstrual rhythm was investigated by daily plasma hormone (estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone) analyses throughout the menstrual cycle, and patients were diagnosed as showing a subnormal profile of progesterone in the early luteal phase or as showing no abnormality. Women with oligomenorrhea and elevated luteinizing hormone levels were diagnosed as having polycystic ovary syndrome primarily on the basis of endocrinology. All patients were treated with a gonadotropin-releasing hormone analog to suppress endogenous luteinizing hormone and follicle-stimulating hormone so that ovulation induction with exogenous gonadotropins could be undertaken as in patients with hypogonadotropic hypogonadism. Interference in the process of ovulation by endogenous luteinizing hormone fluctuations was eliminated and pregnancies were achieved. The pregnancy rate in the group with polycystic ovary syndrome was 77% per treatment course (six cycles) while that in the group with subnormal progesterone profiles was 61.5%. Patients showing no abnormality achieved no pregnancy, demonstrating the redundancy of interference with normal ovarian function.

The effect of exogenous hormones on the resistance of the early pregnant human cervix.

Summary. The force required to dilate the cervix to a diameter of 8 mm (cervical resistance index) has been measured in 355 patients undergoing suction termination in the first trimester of pregnancy. The cervical resistance index (CRI) was significantly lower in multigravid patients compared with primigravid patients. Prior treatment with prostaglandin E2 pessaries produced a consistent reduction in CRI in multigravidae but not in primigravidae. The effect of the prostaglandin was more pronounced on the compliance of the cervical tissue than on the diameter of the cervical canal. Treatment with pessaries of oestradiol, progesterone and medroxy‐progesterone acetate produced no changes in the CRI.

Luteal phase deficiency: ultrasonic and biochemical insights into pathogenesis

Summary. Serial ovarian ultrasound and daily assessments of plasma concentrations of pituitary and ovarian hormones were used to investigate ovarian function in 175 women with unexplained infertility. Their endocrine and ultrasound profiles were compared with similarly derived data from 43 normal volunteers. Fifty‐one (29·1%) of the study group showed subnormal luteal phase rises in progesterone concentrations, described as poor progesterone surge (PPS) cycles. Within this group, 23 women (45·1%) demonstrated luteal cyst formation, a pattern not seen in any of the control cycles. High concentrations of follicle stimulating hormone (FSH) and reduced concentrations of oestradiol (E2) were observed in the follicular phases of the PPS cycles suggesting that the phenomenon is a product of abnormal follicular metabolism. An association of PPS with infertility exists, perhaps related to a combination of disturbances in the follicular micro‐environment compromising oocyte quality, a failure of oocyte release, and impaired endometrial receptivity.

'Unexplained infertility’results of secondary investigations in 95 couples

Abnormalities of in‐vitro sperm‐mucus penetration, ovarian hormone deficiency, specifically poor progesterone surge, and luteal cyst formation were assessed prospectively in 95 couples with fully investigated primary infertility of 3·3 years duration. Abnormal spermmucus penetration was found in 22, half of whom could have been identified on semen assessment alone. Ten other males had recurrent oligospernia but with normal motility and mucus penetration. Twentyone patients had a poor progesterone surge and seven of them demonstrated retained luteal phase cysts. Endocrine and mucus penetration abnormalities did not coincide, demonstrating that they are distinct and unrelated phenomena. A significant number of couples were found for whom the term‘unexplained infertility’was no longer applicable and appropriate management could be considered.

Combined Buserelin and Exogenous Gonadotrophin Therapy for the Treatment of Infertility in Women with Polycystic Ovarian Disease

A considerable proportion of the women who attend infertility clinics menstruate but do not show normal menstrual rhythm. 01igomenorrhea (menstrual cycles occurring at >6 week intervals) was found in 16% of 1,162 new patients attending the Infertility Clinic at Glasgow Royal Infirmary during the years 1975–1983 [1]. The exact status of such patients with respect to ovarian function is difficult to assess since menstruation, when it occurs, although obviously a response to hormone withdrawal may or may not be associated with a preceding ovulation. In this chapter the results of in-depth investigations on 55 infertile women with oligomenorrhea are presented.

Combined Buserelin and Exogenous Gonadotropins in Ovulation Induction in Infertile Women with Normal Menstrual Rhythm

Infertility amongst women with normal menstrual rhythm, normal pelvic anatomy and normal patterns, is a common and complex clinical problem requiring a comprehensive approach. There are many areas of debate concerning the relative importance of different alleged pathologies and the efficacy of treatments directed at them. It is for these reasons that a strict approach to patient definition and selection should be maintained, although there is no universally adopted systematic approach to either.