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One-hundred women undergoing ovarian stimulation with gonadotrophin-releasing hormone agonist (GnRH-a) and a human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF) participated in this randomized comparative study. The effectiveness of long-acting s.c. goserelin (Zoladex depot; 49 patients) and intranasally (i.n.) administered buserelin acetate (Suprefact; 51 patients) for pituitary down-regulation was compared. Treatment with s.c. goserelin (3.6 mg) or i.n. buserelin acetate (200 micrograms; 6 times/day) was started on day 21-23 of the cycle. Stimulation with 150 IU of HMG/day was started after at least 11 days of GnRH-a treatment. There were no differences in the time required for follicular development nor in the clinical outcome between groups treated with either goserelin or buserelin. The number of oocytes recovered in the goserelin group was 6.7 +/- 5.0 versus 6.3 +/- 4.9 in the buserelin group. There were 11 pregnancies after the use of goserelin (22.4%) and 12 pregnancies in those given buserelin (24.0%). The number of HMG ampoules needed for follicular maturation was higher in the goserelin group (27.9 +/- 7.8) than in the buserelin group (24.6 +/- 7.8, P < 0.05). The patients given buserelin suffered significantly more from tiredness, depression, headache and abdominal pain than those receiving goserelin, whereas there were no differences between the groups in experiencing mental irritability, nausea and swelling. Subcutaneous goserelin depot injection offers a useful alternative for pituitary down-regulation in IVF stimulation.

Infertility due to obstructive azoospermia in 24 men was treated with a combination of scrotal exploration, microsurgical sperm aspiration and vasoepididymostomy, at the same operation. In-vitro fertilization (IVF) and embryo transfer were performed using epididymal spermatozoa. Donor spermatozoa were used if no motile epididymal spermatozoa were obtained. With this combination, emotionally and economically acceptable pregnancy rates were achieved: 24% per aspiration, 43% per embryo transfer, and 25% per couple. One twin pregnancy resulting in the birth of two healthy female infants and one ongoing twin pregnancy were achieved with epididymal spermatozoa; four pregnancies (one twin, two singletons, one abortion) were achieved with donor spermatozoa.

To study whether balance between antiaggregatory, vasodilatory prostacyclin (PGI2) and proaggregatory, vasoconstrictory thromboxane A2 (TXA2) could be affected by dietary manipulation, 18 pre-eclamptic women were treated in randomized order between 31 and 36 weeks of gestation either with primrose oil (n = 7), with fish oil (n = 5), or with placebo (n = 6). Urinary excretions of the degradation products of PGI2 (6-keto-PGF1 alpha, 2,3-dinor-6-keto-PGF1 alpha) and TXA2 (TXB2, 2,3-dinor-TXB2) were measured in 24 h urines before and serially during the supplementation. Fatty acid supplementation did not affect urinary prostanoid excretions or clinical signs of pre-eclampsia.

The effect of ovulation induction on serum insulin-like growth factor binding protein 1 (IGFBP-1) level in relation to sex hormone binding globulin (SHBG) levels was evaluated. Serum samples were collected 8 to 12 days after ovulation from 26 women undergoing ovulation induction with clomiphene citrate (CC), and from 58 women treated with CC in combination with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). In addition, serum samples were obtained from 63 spontaneously ovulating women and from 12 women during an anovulatory cycle. Luteal phase serum IGFBP-1 levels were 4.22 +/- 2.95 micrograms/L (P less than .05) in the CC group and 7.31 +/- 6.13 micrograms/L (P less than .001) in the CC/hMG/hCG group as compared to unstimulated ovulatory cycles (2.64 +/- 2.52 micrograms/L). No significant difference in IGFBP-1 levels was seen between spontaneously ovulatory and anovulatory cycles. The serum IGFBP-1 levels correlated positively to SHBG levels (r = .52, P less than .001). The data show that ovulation induction increases serum IGFBP-1 levels in parallel to SHBG levels, indicating that ovarian stimulation, which results in increased steroid hormone production, also induces changes in other factors known to modulate steroid hormone actions.

Detection of sperm surface antibodies is important for the diagnosis and treatment of infertility. The authors have investigated the methodologic aspects of flow cytometry (FCM) to detect sperm-bound antibodies and to quantitate the sperm antibody load (antibody molecules/spermatozoa). To obtain reliable results, dead spermatozoa must be excluded from analysis because they can bind antibody nonspecifically, and comprise 10% to 58% (n = 28) of the ejaculate in subfertile men. Flow cytometry estimation of dead cells correlates (r = 0.83) significantly with the manual Eosin Y method. After staining washed sperm samples (n = 26) with fluorescein-isothiocyanate-conjugated F(ab')2 fragments of anti-IgG and IgA antibodies, the sperm load was 11,500 +/- 8,600 IgG molecules and 13,200 +/- 9,500 IgA molecules per spermatozoa. The sperm antibody load measured on different occasions could be compared between patients or in the same patient by the use of calibration standards. Since the inter- and intra-assay variation of the FCM assays was less than 10%, FCM has the potential reliably and objectively to monitor the sperm antibody load during corticosteroid treatment.

Thirty-five women who had been operated on for mild or moderate endometriosis were evaluated through 40 menstrual cycles by daily measurements of salivary progesterone concentrations. As controls, 17 women with normal ovulatory cycles and no endometriosis were studied. In the endometriosis group, 22 cycles were unstimulated, seven were stimulated by clomiphene citrate and 11 with clomiphene citrate, human menopausal gonadotrophin and human chorionic gonadotrophin. A variety of aberrations in profiles of salivary progesterone secretion was detected in all the groups of endometriosis patients and the frequency of normal cycles was significantly lower than in controls (14-18% versus 82%, P less than 0.01). The response to the treatments varied greatly within the groups. In conclusion, the present data demonstrate that patients with endometriosis have a variety of defects in the menstrual pattern of salivary progesterone secretion and that their corpus luteum function responds poorly to stimulatory treatments.

Forty-five women suffering from unexplained infertility collected saliva for progesterone (P) measurements every morning during 1 to 3 complete cycles. A total of 27 cycles analyzed were unstimulated, 19 were stimulated by clomiphene citrate (CC), and 7 with CC, human menopausal gonadotropin (hMG), and human chorionic gonadotropin (hCG). Compared with reference profiles of salivary P from 27 normal cycles, the length and magnitude of P secretion were significantly lower in the infertility group. Luteal P concentrations were normalized during CC stimulation and significantly elevated during the CC-hMG-hCG stimulation. The other abnormalities found in the salivary P profiles of these patients included preovulatory P peaks, interruption of P secretion during luteal phase, and high P level at the beginning of menstruation. The results suggest that patients with prolonged unexplained infertility represent a heterogenous population with common luteal phase defects. The disturbance is effectively corrected with treatments stimulating gonadotropin secretion.

Direct intraperitoneal or intrauterine insemination in combination with superovulation was used randomly as the treatment of infertility that was unexplained or due to male subfertility or mild endometriosis in 124 couples during 326 cycles. The pregnancy rate per couple was 24% in the direct intraperitoneal insemination group and 31% in the IUI group. The difference was not significant. The pregnancy rates with both treatments were significantly higher than those seen during the 326 control cycles of the same couples (1.1% and 0.6%).

Immunoperoxidase staining and radioreceptor assay were used to study the localization of LH, FSH, and PRL and their receptors in the human and rat testis. In immunohistochemical staining, the Leydig cells of both species were invariably LH positive and generally FSH negative, but there were some FSH positive cells which were morphologically indistinguishable from the Leydig cells. The tubules were LH negative. The Sertoli cells of both species were FSH positive, whereas the spermatogonia and other germ cells were negative. Positive staining for PRL was seen in rat Leydig cells, whereas the human testes were negative. In keeping with the immunohistochemical findings, LH and FSH receptors were found in the testis of both species, but PRL receptors only in the rat. The finding of FSH positive cells in the interstitial tissue may explain why FSH increases the number of Leydig cell LH receptors and increases the sensitivity and maximum response to LH stimulation. Failure to demonstrate PRL and PRL receptors in the human testis indicates either that very low receptor concentrations are needed to bring about PRL action or that the established testicular effects of PRL are indirect.

A double blind controlled study of bromocriptine treatment of oligospermia was carried out. Out of fifty-one men who originally volunteered to the study there were forty who took the drug for 12 weeks as requested. All the partners of these men had failed to conceive, and in each case the pretreatment sperm count had been below 40 million/ml on two or several occasions. The pretreatment serum prolactin concentrations were similar in patients given bromocriptine (N = 20) and placebo (N = 20). There were three men in either group whose pretreatment serum prolactin concentration was in excess of 30 micrograms/l, the highest value being 96 micrograms/l. While bromocriptine effectively decreased the serum prolactin concentration, it had no significant effect over placebo on sperm volume, motility and morphology. In the bromocriptine group, sperm count increased to or above 40 million/ml in five out of twenty men, while in the placebo group this occurred in nine out of twenty patients. The plasma testosterone and dihydrotestosterone levels increased slightly during treatment in both groups, but no significant difference was observed between bromocriptine and placebo treated patients. One wife of a bromocriptine-treated man and two wives of placebo-treated men became pregnant during treatment. In this study bromocriptine was no more effective than placebo in the treatment of oligospermia.

Antisperm antibodies were tested for by the MAR-test and the tray agglutination test in 16 men with spinal cord injury. None of these men could ejaculate without artificial methods. Seven men ejaculated externally by vibrator stimulation or electroejaculation, while seven exhibited retrograde ejaculation; in two cases no semen was obtained. Sperm density in the external ejaculations was high (average = 405 x 10(6)/ml), with 10-45% motility. None of these 16 men had antisperm antibodies. This result indicates that anejaculation and sperm retention in men with spinal cord injury, even of 30 years duration, does not result in antisperm antibody formation.

Daily concentrations of salivary progesterone (P) were measured from 32 women during a complete menstrual cycle. Seventeen of the subjects were university students and 15 were patients of an infertility clinic (a severe male-factor was verified as the cause of infertility in all of them). Commercially available reagents for radio-immunoassay of serum P were modified for salivary measurements, to yield acceptable precision and sensitivity (40 pmol/l). Good correlation (r = 0.93) was found between salivary and serum P concentrations in samples collected simultaneously. The follicular phase levels of salivary P were below 100 pmol/l, and those at the luteal peak were 390 +/- 45 pmol/l (mean +/- SEM, n = 24). From the menstrual salivary P concentration curves we identified the first day of significant elevation above mean follicular levels (T2) and thereafter calculated the cumulative sum of daily P concentrations until 95% of the luteal phase secretion had accumulated (C95). The time needed to reach C95 (designated T95) and logC95 were plotted in coordinates and used as the basis of evaluation of normal menstrual P secretion. The observations were distributed in two groups, one with clearly identifiable T2 and a distinct luteal-phase P (ovulation had occurred) and one with no identifiable T2 and absent luteal-phase P peak (indicative of anovulation). Interestingly, 47% of the student population had an abnormally low menstrual P profile while all the other subjects displayed a clear luteal-phase peak of salivary P. These data provide more evidence for applicability of salivary P measurements for diagnosis of corpus luteam function and highlight the difficulty of selecting representative reference populations in studies on female reproductive endocrinology.

Prolactin concentration was estimated by radioimmunoassay in seminal plasma and serum of 26 oligospermic and 23 normospermic men. No significant difference was found in the mean serum prolactin concentration between normospermic and oligospermic subjects, but there was an inverse correlation between serum prolactin level and sperm count within the group of oligospermic patients. Although the mean prolactin concentration in seminal plasma of oligospermic group was somewhat lower than in the normospermic group the difference did not reach statistical significance, and no correlation was found between seminal plasma prolactin concentration and sperm count within either group.

The clinical and autopsy findings in all stillbirths during the years 1974-1979 at the Helsinki University Central Hospital were analysed. There were 243 stillborn infants of whom 200 died before labour. According to the autopsy findings asphyxia accounted for 38% and major malformations for 17% of the deaths, but because of fetal maceration no diagnosis could be made at autopsy in 43%. The cause of death suggested by the clinical findings was placental failure in 57%, cord complication in 12% and major malformations in 17%. The cause of death remained unsolved in 9%. The importance of routine ultrasound and alpha-fetoprotein screening for the detection of unrecognized risk patients is emphasized.

The localisation of endogenous FSH and LH was studied in 4 inguinal adult human testes by the immunoperoxidase technique utilising antisera against the beta-subunits of human FSH and LH. The content of available FSH and LH receptors was determined by radioreceptor assay. The Sertoli cells and about 10% of cells in the intersitium the Leydig cells, possibly the testicular macrophages, were similarly FSH-positive in cryptorchidism and control testes. The FSH receptor levels per testis were significantly lower in cryptorchidism than in control testes. Also the localisation of LH in Leydig cells in cryptorchidism was similar to the control testes, but the LH receptor level was significantly lower. These data bring further evidence for Leydig and Sertoli cell malfunction in the inguinal human testis.