Polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy, affecting 5-10% of the female population. It involves overproduction of ovarian androgens leading to a heterogeneous range of symptoms including hirsutism, acne, anovulation and infertility. Hyperinsulinaemia, exacerbated by obesity, is often a key feature. Treatment depends on the presenting symptoms, which may often be ameliorated by weight loss where relevant. Anti-androgen preparations are used for hyperandrogenic symptoms, and clomiphene citrate (CC) is the first-line treatment for anovulation and infertility. Aromatase inhibitors are being investigated as an alternative to CC. Failure to conceive with CC can be treated in a number of ways, including the addition of insulin-lowering agents (mainly metformin), low-dose gonadotrophin therapy or surgically by laparoscopic ovarian drilling. Although the exact aetiology of PCOS is not known, the therapeutic alternatives provide reasonably successful symptomatic treatment.

Characteristics of an antiluteinizing hormone isoantibody produced during gonadotropin induction of ovulation.

Production of an antihuman LH antibody was suspected in a woman with isolated LH deficiency who received human pituitary gonadotropin (hPG) to induce ovulation and who developed secondary drug failure associated with very high "serum LH' values. Binding of [125I]LH to various dilutions of the patient's serum was demonstrated by precipitation with polyethylene glycol or sheep antihuman immunoglobulin G (anti-IgG) but not by precipitation with sheep antihuman immunoglobulin M (anti-IgM). Unlabeled LH competitively displaced [125I]LH from a 1:200 final dilution of the patient's serum, and indicated a single class of binding sites with a binding affinity of 1.5 X 1011 M-1 and a binding capacity of 84 ng LH/ml serum. The isoantibody was reactive against antigenic determinants in hPG, LH, and hCG but not against human FSH. Further examination showed binding to the beta, but not the alpha, subunit of two LH preparations and to beta hCG. It is concluded that repeated administration of hPG to this patient with isolated LH deficiency evoked IgG isoantibody formation against the beta subunit of LH.

Short- and long-term effects of ovulation induction.

Ovulation induction using clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone is reviewed. The short- and long-term consequences of these therapies are discussed in detail.

Estrogen excretion patterns in induced ovulation.

Observation of response to gonadotropins in the treatment of anovulation has allowed us to define the estrogen excretion pattern which leads to a successful single pregnancy. The typical pattern shows a low pretreatment urinary total estrogen excretion; treatment with gonadotropins, of human pituitary origin, is continued for about 14 days. There is a predictable rate of rise of preovulatory estrogen excretion (30 microgram/24 hr2). Human choronic gonadotropin--about 4000 IU--should be given when an estrogen excretion of 75-100 microgram/24 hr has been obtained. The use of this pattern of ovarian response is put forward as a useful guide in the planning of gonadotropin therapy.

The value of ovarian biopsy in the diagnosis and treatment of amenorrhea-related sterility.

PIP: 16 patients aged 23-38 suffering from primary or secondary sterility due to oligomenorrhea or amenorrhea had ovarian biopsies performed by surgical culdoscopy using Clyman's method. The technique was useful in diagnosing 8 cases of premature menopause. In the other patients the surgical culdoscopy approach was superior to ordinary culdoscopy for evaluating ovarian structure and changes due to the ovulation stimulants chlomiphene and Pergonal.^ieng

Pregnancy in women with Kallmann's syndrome.

OBJECTIVE: To induce of ovulation and pregnancy in women with Kallmann's syndrome. DESIGN: Retrospective study. PATIENTS: Three women with hypogonadotropic hypogonadism and anosmia with a desire for pregnancy. INTERVENTIONS: Investigation of hypothalamic-pituitary-ovarian function and induction of ovulation by pulsatile GnRH or intramuscular human pituitary gonadotropins (hPG) or hMG with hCG. MAIN OUTCOME MEASURES: Successful induction of ovulation as measured by serum P levels and successful pregnancy. RESULTS: Ovulation was induced successfully in all three patients on more than one occasion and nine pregnancies occurred. Gonadotropin-releasing hormone was given IV by an electronically timed syringe driver. A total of 12 pulsatile GnRH cycles resulted in two pregnancies, 6 of these cycles being in one patient who did not ovulate or conceive with this therapy. Ovulation occurred in 10 of 16 hMG or hPG cycles, with conception in 7 of these. Gonadotropin usage was higher in these women compared with women with hypogonadotropic hypogonadism without anosmia (2,850 compared with 2,100 IU per treatment cycle), and the follicular phase was longer. CONCLUSIONS: All three women conceived and had children after induction of ovulation. The success rate of these therapies in Kallmann's syndrome appears to be high in spite of very few reports in the literature.

Effects of preceding androgen therapy on testicular response to human pituitary gonadotropin in hypogonadotropic hypogonadism: a study of three patients.

There is some uncertainty about the choice of initial therapy to induce virilization in men with hypogonadotropic hypogonadism (HH) who may subsequently desire fertility. Three patients with HH and azoospermia are described. All had received long-term androgen therapy in fully virilizing doses, and two also received interval androgen therapy. Spermatogenesis occurred in all three patients after treatment with human chorionic gonadotropin and human pituitary gonadotropin, and the wives of all three conceived. For two patients conception occurred three times in response to gonadotropin therapy, and libido and potency were maintained with testosterone between each conception. It is concluded that preceding long-term therapeutic doses of androgen do not impair subsequent induction of spermatogenesis in patients with HH.

A low sperm concentration does not preclude fertility in men with isolated hypogonadotropic hypogonadism after gonadotropin therapy.

In order to define the minimal number of sperm needed for conception, we studied semen characteristics of men with isolated hypogonadotropic hypogonadism (IHH) who became sperm-positive during gonadotropin therapy. Twenty-two of 24 men (92%) proved fertile, initiating a total of 40 pregnancies. The mean (+/- standard error of the mean) sperm concentration at the time of conception was 16.7 +/- 4.0 X 10(6)/ml. However, 71% of pregnancies were conceived when the mean sperm concentration was less than 20 X 10(6)/ml; in 16%, the mean sperm concentration was less than 1 X 10(6)/ml. Mean total sperm count correlated highly with sperm concentration (r = 0.67, P less than 0.001). We conclude that men with IHH can initiate conception even when their sperm concentration is well below the conventional lower limit of 20 X 10(6)/ml.

Levels of steroid and protein hormones in antral fluids of women treated with different combinations of gonadotropins, clomiphene citrate, and a gonadotropin-releasing hormone analog.

Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone (P), and total protein in follicular fluids collected from 18 patients pretreated with a gonadotropin-releasing hormone analog (GnRHa), in association with human menopausal gonadotropin (hMG) and FSH, were compared with values for 69 patients treated with FSH, hMG, FSH/hMG, or clomiphene citrate (CC)/hMG in an in vitro fertilization (IVF) program. The authors have established a number of significant differences in chemical and physical properties of follicular fluids of patients treated by different regimen, and concur with earlier evidence that the volume of a follicle, and its P and total protein content, are related to the maturity of the oocyte nested within the follicle. Overall, however, differences in concentrations of gonadotropins in follicular fluids between groups were not consistent with differences in follicular fluid steroid levels, and levels of immunoactive gonadotropins in follicular fluids were not in accord with dosages of exogenous immunoactive gonadotropin administered during hyperstimulation. The most favorable outcomes of IVF (greater than 70% of oocytes fertilized) were established with oocytes collected from patients treated with FSH only or with CC/hMG, and patients treated with FSH only yielded the highest average number of oocytes which fertilized in vitro (6.2 per patient).

A normal cumulative conception rate after human pituitary gonadotropin.

Forty consecutive women were treated with human pituitary gonadotropin to induce ovulation. Thirty-seven patients (93%) ovulated and thirty (75%) conceived on at least one occasion. The cumulative conception rate for the series equaled that of the general population. Women with a past history of anorexia nervosa had the shortest average time to pregnancy. Of patients who did not conceive, four represented failures of patient selection in that they withdrew from treatment for a variety of psychiatric and social reasons, and six represented failures of treatment, not becoming pregnant despite the induction of ovulation. It is concluded that realistic goals for a contemporary human gonadotropin program include induction of ovulation in all patients and a cumulative conception rate equal to that of the general community.

Gonadal function and response to growth hormone (GH) in boys with isolated GH deficiency and to GH and gonadotropins in boys with multiple pituitary hormone deficiencies.

OBJECTIVE: [corrected] To evaluate spermatogenesis in patients with isolated GH deficiency and multiple pituitary hormone deficiencies. DESIGN: Treatment of isolated GH-deficient patients with recombinant human GH (weekly dose of 0.7 IU/kg) for 5.3 +/- 0.4 (mean +/- SD) years and cotreatment of multiple pituitary deficient patients with GH at the same dosage for 8.0 +/- 0.4 years and hCG (2,000 IU, three times per week) and hMG (500 IU, two times per week) for 13.7 +/- 1.1 months. SETTING: Endocrine Pediatric Unit. PATIENTS: Eight patients affected by isolated GH deficiency and seven by multiple pituitary hormone deficiencies. MAIN OUTCOME MEASURES: Serum LH, FSH, and T, testicular volume, semen volume, density, count, and motility. RESULTS: Patients with isolated GH deficiency completed their pubertal development in 19.0 +/- 3.5 months and patients with multiple pituitary hormone deficiencies in 13.7 +/- 1.1 months. At the end of puberty, the two groups of patients had similar testicular volume, penis size, sperm concentration, motility, and morphology, although T levels and seminal volume were lower in isolated GH-deficient patients than in multiple pituitary deficient patients. CONCLUSIONS: The two groups of patients, treated specifically for their identified hormonal deficiencies, in the end had similar satisfactory reproductive results.

Secondary amenorrhoea after oral contraceptives - treatment and follow-up.

PIP: 103 women with secondary amenorrhea subsequent to oral contraceptive (OC) therapy were studied with regard to previous menstrual history, duration of OC therapy, prospects of spontaneous cure, treatment repsonse, and induced pregnancy's effect on later menstrual pattern. 73 of the 103 patients had regular 26-to-35 day cycles before treatment, and 81 of the 103 had 0 parity. 72 had taken OCs 3 to 24 months with 76 having subsequent amenorrhea of 12 to 23 months. 12 of 22 patients on OCs 25 to 36 months had amenorrhea of 36 months or more. 84 patients had taken 19-nor-gestogen type combination OCs. 61 patients were treated with clomiphene citrate and 34 appeared to ovulated with 24 pregnancies resulting in 22 patients. 7 patients not responding to clomiphene citrate ovulated in response to human pituitary gonadotropin; 4 patients had 6 pregnancies. Follow-up reveals 31 women with persistent amenorrhea, 35 with spontaneous cure, 12 with spontaenous cure after induced pregnancy. The author concluded that induced pregnancy has only a chance effect on ultimate prognosis.^ieng

Quintuplet pregnancies.

Five quintuplet pregnancies, following induction of ovulation with clomiphene and HMG-HCG, are the subject of this communication. In 3 women, pregnancy was associated with ovarian overstimulation, and two patients required emergency surgery because of torsion of an ovarian cyst. Two women aborted in mid-trimester, while the other 3 delivered by cesarean section at 33-35 wk gestation. 15 babies were born, weighing 700-2200 g. 8 infants suffered from respiratory distress syndrome and 5 babies were born with correctable malformations. 13 newborns survived, and all are mentally and physically well-developed. Four of the 5 women conceived again. The management of the patients during multiple gestation and the outcome of pregnancy are discussed.

Ultrasound and ovulation.

Diagnostic ultrasound may be used to both investigate unexplained infertility and monitor all types of infertility treatment in women. Presented in this paper are the numbers of cycles scanned and the numbers of scans performed over the period from November 1981 to March 1986. In patients with unexplained infertility there was only a 39% rate of normality observed with ultrasound. Ultrasound observation of ovulation in patients on clomiphene or gonadotrophin therapy showed a disappointingly low rate.

Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments.

The aim of this study was to compare endocrine changes and the follicular development in patients receiving pure FSH alone or in association with LH after desensitization with an LH-RH agonist depot. Thirty four cycles were selected for this prospective randomized study. Desensitization was obtained using Goserelin the cycle before the stimulation. Induction of ovulation for IUI was carried out with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and ampules required for follicular maturation were equivalent in the two groups. The same number of follicles were developed, while different, but not significant, pregnancy rates were obtained. Estradiol values at the end of stimulation were significantly lower for FSH group. In conclusion the contemporary administration of LH with FSH does not exert any effect on follicular development, but it seems to facilitate E2 synthesis, probably providing more substrate for the aromatization process.

[Disappearance of migraine crises in two patients with male infertility treated with human chorionic gonadotropin/human menopausal gonadotrophin]. / Desaparición de crisis migrañosas en dos pacientes tratados con hCG/hMG por infertilidad masculina.

Two patients aged 52 and 31 respectively, treated for male infertility with gonadotrophins (LCG/LMG), showed marked improvement of their migraine crises associated with a typical aura which had been present since puberty. Changes in the number, motility and morphology of the spermatozoids were seen in the seminogram. The plasma concentrations of FSH, LH, testosterone an 17-beta oestrodiol were within normal limits. After three months of empirical treatment with LCG/ LMG (to stimulate spermatogenesis) the migraine crises ceased and the patients are still free of migraine after 32 and 26 months respectively. The relationship between migraine and the sex hormones is discussed, in the context of current knowledge of the psysiopathology of migraine and the beneficial effects obtained after treatment with LCG/LMG. We have not found any reference in the literature to the use of gonadotrophins in the treatment of migraine with a typical aura.

[Treatment in male infertile clinic of Kaizuka Municipal Hospital].

The results of treatment of 68 idiopathic male infertile cases are reported. The follow up period was 3 years and 8 months from the time the Department of Urology, Kaizuka Municipal Hospital had opened. The main treatments were human mammary gonadotropin-human chorionic gonadotropin (HMG-HCG) therapy and high ligation of left testicular vein in the cases accompanied with varicocele. Adjuvant therapy was administration of vitamin B12, herb medicine and antibiotic agents for prostatovesiculitis. Some cases were administered clomiphene citrate. The results in 43 cases at over 10 weeks after treatment was followed. Mean sperm count and mean sperm activity rate in 11 cases accompanied with no varicocele and whose sperm count was 2 approximately 45 x 10(6)/ml were raised from 11.0 +/- 8.0 SD x 10(6)/ml and 19.1 +/- 11.4 SD% to 22.7 +/- 16.8 SD x 10(6)/ml and 26.9 +/- 18.5 SD%, respectively after 20 weeks of HMG-HCG therapy. Efficacy was 7 out of 11 (63.6%) in sperm count and 6 out of 11 (54.5%) in sperm activity rate. Pregnancy was obtained in 3 cases. Effect of HMG-HCG therapy was not observed in 8 cases accompanied with varicocele and whose sperm count was 2 approximately 45 x 10(6)/ml. High ligation of left testicular vein was effective in all of the 4 cases accompanied with varicocele and whose sperm count was 2 approximately 45 x 10(6)/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Kallmann's syndrome: reproductive success.

Kallmann's syndrome is a genetic disorder that includes pituitary gonadotropin deficiency associated with sexual immaturity and infertility. A successful treatment program resulted in normalization of sexual development, spermatogenesis, and conception.

Are human male patients with DAX1/NR0B1 mutations infertile?

DAX-1 stands for Dosage sensitive sex-reversal, Adrenal hypoplasia congenital (AHC), on the X chromosome. DAX-1 mutations usually cause primary adrenal insufficiency or congenital adrenal hypoplasia in early childhood and hypogonadotropic hypogonadism (MIM # 300200). DAX-1 protein is necessary to maintain normal spermatogenesis. In humans, male fertility has been studied in few patients carrying DAX-1 mutations. Cases of azoospermia have been reported, as well as unsuccessful gonadotropin treatments. The clinician should be informed that TESE-ICSI technique carries a potential hope to father non-affected children, as shown in this review.