Pregnancy outcome in luteinizing hormone-releasing hormone induced cycles: a multicentre study.

In a retrospective international study 223 pregnancies induced with pulsatile hormone-releasing hormone (LH-RH) were evaluated. In patients with hypothalamic amenorrhea (HA) and polycystic ovarian disease (PCOD) the abortion rate was similar (10% vs 8.7%). The premature delivery rate was significantly higher, however, in the patients with HA, but this could be explained by the higher incidence of multiple pregnancies in this group. Thirty multiple pregnancies were observed in the HA group (n = 174) compared with none in the PCOD group (n = 24; p less than 0.05). The incidence of multiple pregnancies in the HA group correlated to the pulse dose (p less than 0.05). The 1st treatment cycle resulted in more multiple pregnancies than did subsequent cycles (p less than 0.05). Difference in pulse interval did not affect the incidence of multiple pregnancies, nor did the route of administration (intravenous or subcutaneous). The incidence of congenital anomalies was comparable to that with spontaneously achieved pregnancies.

The role of the laboratory in the investigation of infertility.

The incidence and the causes of the various types of infertility in men and women are described. Accurate diagnosis of the cause or causes of a couple's infertility is important as the treatment is often expensive and lengthy. A thorough clinical investigation of the couple will indicate which laboratory tests to embark upon. Endocrine abnormalities may account for about a third of diagnoses in women but are rare in men. Standard immunoassay procedures are used for hormone assays to diagnose endocrinopathies and should be performed in a logical sequence. They help to identify hyperprolactinaemia and to distinguish primary gonadal failure from lesions of the hypothalamic-pituitary axis. The common drugs available for treatment are listed and guidelines are given on management during treatment. Hormone assays are useful, but ultrasonic scanning is efficient and rapid and is becoming the preferred method for monitoring follicular growth.

Pulsatile GnRH therapy for the induction of ovulation in hypogonadotropic hypogonadism.

Twenty-eight patients with hypogonadotropic hypogonadism resistant to clomiphene therapy were treated with pulsatile GnRH. All the patients ovulated and there were 20 pregnancies in 16 women. Administration of the GnRH sc was successful at inducing ovulation in 19 of 22 patients whereas the treatment was successful in all of the 17 patients treated iv. There was no difference between iv and sc therapy in the rate of ovulation. Treatment was stopped after ovulation and hCG given for luteal support. The follicular phase pulse frequency was usually 90 min. In one patient ovulation only occurred with frequencies of 60 min. Higher pulse doses were usually required with sc therapy for primary amenorrhoeic patients and for those with pituitary lesions. The additional use of clomiphene increased pituitary sensitivity to GnRH resulting in ovulatory cycles in patients refractory to treatment and in ovarian hyperstimulation in a normally responsive patient. Two of the 20 pregnancies were twin--the rest were singletons. None aborted. The median time to conception was 3 ovulatory cycles. Although there were no serious complications with iv or sc therapy, the iv route is now reserved for those patients unresponsive to sc treatment as the sc route is potentially safer and more acceptable to the patient. In correctly selected patients pulsatile GnRH is a highly effective and safe new treatment for the induction of ovulation.

Effect of injection site on the pharmacokinetics and pharmacodynamics of subcutaneously administered luteinizing hormone releasing hormone.

Serum concentrations of LHRH and the subsequent LH responses were compared following s.c. injections of 20 micrograms LHRH into the upper arm and the lower abdominal wall, in 9 hypogonadal women responsive to pulsatile LHRH therapy. Tests were carried out at the two sites in random order. Peak LHRH concentrations were reached by 5 min after upper arm and by 20 min after lower abdominal wall injections, the maximum concentrations being significantly greater following injections into the former. There was no increase in LH until 10 min and then maximum concentrations were reached at 30 min following injection into both sites. There was no significant correlation between the LHRH increments and the LH response but there was a negative correlation between the Ponderal Index of the patients and the LHRH increments following injections into the lower abdominal wall only. There was no significant overall difference between the LH increments related to the site of injection, but the order of injections affected the responses. When upper arm injections were given first the LH responses were significantly greater, but when lower abdominal wall was injected first the subsequent responses to upper arm injections were impaired. A possible reason for this is that the absorption from the lower abdominal wall was delayed so prolonging the exposure of the pituitary gonadotrophs to LHRH, resulting in pituitary desensitization at the time of the second test.