Valerie Little

Unexplained infertility—the value of Pergonal * superovulation combined with intrauterine insemination

Sixty-two women with unexplained infertility were studied. Fifteen (group 1) had timed intrauterine insemination (IUI), 25 (group 2) were treated by Pergonal (Serono Laboratories, Ltd., Welwyn Garden City, England) superovulation, and 22 (group 3) underwent Pergonal superovulation combined with IUI. Where Pergonal treatment was followed by insemination, a significantly greater pregnancy rate per cycle (P less than 0.05) was achieved, whether this group of patients was compared with those treated by IUI alone or with those treated with Pergonal alone. Moreover, the pregnancy rate in group 3 was comparable to that reported following gamete intrafallopian transfer (GIFT). The authors therefore suggest this form of treatment for patients with unexplained infertility prior to their referral to the more invasive procedure of GIFT.

Induction of Ovulation in Women with Hyperprolactinemic Amenorrhea Using Clomiphene and Human Chorionic Gonadotropin or Bromocriptine

Clomiphene citrate (Clomid), when given alone, is generally considered ineffective in inducing ovulation in women with hyperprolactinemia. This study reports the treatment of 29 infertile women with hyperprolactinemic amenorrhea. Twenty-one patients (eighteen of whom had previously had no ovulation response to Clomid alone) were treated with a combined regimen of Clomid (100 to 200 mg/day for 5 days) and two injections of 5000 IU of human chorionic gonadotropin (HCG), the first 8 to 10 days after Clomid withdrawal and a second injection 1 week later. Basal body temperature charts, conception, and/or plasma progesterone measurements showed that 19 patients ovulated (90%). There were 17 pregnancies in 12 of 21 patients (57% pregnancy rate) with 15 single live births and two abortions. When bromocriptine (Parlodel) became available, a total of 22 patients (including 14 patients previously treated with Clomid/HCG, six of them successfully) with amenorrhea associated with hyperprolactinemia were treated with this drug with dosages varying from 2.5 mg to 15 mg/day. Ovulation was confirmed in 20 patients (90%). There were 17 pregnancies in 15 patients (68% pregnancy rate) with 15 single live births and two first-trimester abortions. In all, 21 of 29 patients (73%) achieved one or more pregnancies resulting in live births with one or both of the above treatments. It is concluded that a combined Clomid/HCG regimen can often be used as an effective alternative to bromocriptine therapy in the treatment of infertility associated with hyperprolactinemic amenorrhea.

INDUCTION OF OVULATION WITH CLOMIPHENE AND HUMAN CHORIONIC GONADOTROPHIN IN WOMEN WITH HYPERPROLACTINAEMIC AMENORRHOEA

Seventeen women complaining of infertility (one with primary amenorrhoea, 14 with secondary amenorrhoea, and two with oligomenorrhoea) all had hyper‐prolactinaemia and were treated with clomiphene citrate and human chorionic onadotrophin (HCG), and plasma oestradiol, FSH and LH levels were measured. Although adequate pre‐ovulatory oestradiol levels were present, the surge of LH was absent until the injection of HCG after which all patients ovulated. There were 12 pregnancies in 9 patients resulting in 10 full‐term livebirths, one premature livebirth and one continuing pregnancy. The relevance of these findings to the possible role of prolactin in amenorrhoea is discussed.

THE MONITORING OF GONADOTROPHIN THERAPY BY PLASMA OESTRADIOL AND PROGESTERONE DETERMINATIONS

Plasma oestradiol and progesterone determinations by competitive protein binding techniques were introduced as a means of monitoring treatment with human gonadotrophins of 32 infertile women with amenorrhoea or severe oligomenorrhoea. Human menopausal gonadotrophin (HMG) was administered on days 1, 3 and 5. Human chorionic gonadotrophin (HCG) was injected on day 8 if the response to HMG stimulation was adequate but not excessive, a second dose being given seven days later.

PROLACTIN AND LUTEAL INSUFFICIENCY

The relationship between mid‐luteal plasma levels of progesterone and prolactin was studied in 75 women with regular menstrual cycles. Eighteen women had normal prolactin (mean 260 ± 51.7 mU/l) and normal progesterone levels (mean 67 ± 21.3 nmol/l). Thirty‐nine women had elevated prolactin levels (mean 850 ± 503 mU/l); progesterone levels were normal in all cases (mean 61 ± 22.3nmol/l). Eighteen women had evidence of luteal deficiency (mean progesterone 15.3 ± 7.7 nmol/l); prolactin levels were normal in all cases (mean 243 106 mU/l). There was no correlation between plasma prolactin and progesterone levels.

PROGESTATIONAL AGENTS AND DISTURBANCES OF PREGNANCY

THE use of hormones, including oestrogens and thyroid hormone as well as progestagens, in disturbances of pregnancy, though now of many years’ standing, is still the subject of controversy. Though their use is widespread it is still largely empirical and has not been established on a scientific basis. The main reason for this is that disturbances of pregnancy during the early months may arise from many causes and hormone deficiency, in the presence of which alone hormone therapy could be expected to prove efficacious, is by no means the only, or indeed the most common, of these causes. Only on the assumption that hormone therapy can do no harm, even if it cannot do good except when hormone deficiency exists, could the widepsread empirical use of hormones in the treatment of threatened and habitual abortion be justified. In fact there are no good reasons for making such an assumption and several cogent ones for taking the opposite view. We do not propose to discuss the requirements which would have to be satisfied in order that an entirely valid trial of the clinical efficacy of hormone therapy of one kind or another in the treatment of pregnancy disturbances could be carried out. Suffice it to say they would be stringent, difficult to meet by any single investigator, and have not yet been met in any published study. If we confine ourselves to progestagen therapy for progesterone deficiency, there is at the outset the problem of demonstrating the presence of such a deficiency, since it follows from what has already been said that only patients with progesterone deficiency ought to be included in a trial of the value of progestagen therapy. This problem is not solved satisfactorily by measurements of pregnanediol excretion, or the examination of vaginal smears or of cervical mucus for ferning. Pregnanediol excretion, as a measure of progesterone production, is subject to a number of qualifying factors on the theoretical side and to severe limitations on the practical side. The time taken to collect a 24-hour urine aliquot and to carry out the determination by a reliable method virtually rules out its use in cases of threatened abortion. Though the vaginal smear shows characteristic appearances in pregnancy, and a low pyknotic index (below 20 per cent) is typical, no one has yet demonstrated convincingly that the pyknotic index is related reciprocally to progesterone production or has shown in what way it is affected by the concomitant oestrogen level. The ferning of cervical mucus, an oestrogen induced phenomenon, though inhibited by progesterone, is undoubtedly an even less precise indication of progesterone deficiency in pregnancy than elevation of the pyknotic index. From several points of view, therefore, we are not well equipped to make precise studies of the value of progestagen therapy in threatened and habitual abortion. The foregoing remarks are made in extenuation of our failure in this paper to contribute basically to the establishment of the value of progestagen therapy. The approach we have adopted to the treatment of our patients has had perforce to have been a somewhat pragmatic one, based on a number of assumptions. The first has been that the pyknotic index does, indeed, offer a useful guide to the progesterone level, a value above 20 per cent being regarded as indicative of progesterone deficiency, particularly when rising ; and second, that a progestagen which lowers a raised pyknotic index in pregnancy is likely to be beneficial. We have considered that the urinary excretion of human chorionic gonadotrophin (HCG) reflects the activity of the trophoblast so that a low and falling HCG excretion implies a dying embryo; we have reason to believe that the

THE TREATMENT OF MILD ADRENAL HYPERPLASIA AND ASSOCIATED INFERTILITY WITH PREDNISONE

Thirty patients with mild post-pubertal adrenal hyperplasia, characterized by raised urinary 17-oxosteroid levels and variable combinations of irregular menses, hirsuties, infertility, and spontaneous abortion, were treated with 2.5 to 10 mg of prednisone per day and all conceived (55 pregnancies). With this treatment, regular, ovulatory cycles occurred immediately in 25 patients, and after two to six months, in the rest. Treatment reduced raised 17-oxosteroid levels to normal and brought about some improvement in hirsuties and acne. Forty-seven pregnancies ended in the birth of liveborn infants; one of these died of prematurity and another had congenital emphysema. One pregnancy was terminated, two were of unknown outcome and five (9.4%) ended in abortion. Before treatment, 20 out of 22 pregnancies (91%) had ended in abortion.

Assessment of Mycoplasmas and Infertility and the Effect of Doxycycline

The role of T-mycoplasmas as pathogens of the urinary and genital systems is still largely undetermined. SHEPARD (1954) first isolated T-mycoplasmas from patients with non-gonococcal urethritis, and since then some surveys have suggested a causal relationship SHEPARD (1960), CSONKA ET AL.(1966), whilst other surveys have not supported this view. TAYLOR-ROBINSON ET AL (1969). With regard to women, marked variation in carriage rate have been noted; with a possible relationship to sexual activity. ARCHER (1968) studied 100 pregnant women, 94 women attending an Infertility Clinic, 98 women in a Geriatric Unit, and 106 nuns in an enclosed order, and found carriage rates of 58,51, 29 and 8 per cent respectively. Similarly, MARDH & WESTROM (1968) found that the carriage of T-mycoplasmas was significantly higher in pregnancy. (68.4% against 45.8% and 55.4% in non-pregnant females and females with signs of genital infection respectively). The possibility of an association between low birth weight and T-mycoplasma infection during pregnancy was considered and investigated by KLEIN ET AL(1969)and investigated and confir ed by BRAUN ET AL(1971) KUNDSIN & DRISCOLL(1970)postulated an aetiological role for T-mycoplasma in human reproductive failure and premature birth. A pathogenic role for genital mycoplasmas was demonstrated by SOLOMAN ET Al(1973)in a review of 11 cases of gynaecological sepsis, 3 due to T-strains, and the remainder M.hominis.