Torbjörn Bergh

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not Invariably so when the degree of obesity is taken into account. We have therefore Investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN Cross‐sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight‐matched controls.

Clinical Assessment of Recombinant Human Follicle-Stimulating Hormone in Stimulating Ovarian Follicular Development Before In Vitro Fertilization

OBJECTIVE To compare the efficacy and the safety of recombinant human FSH (hFSH) with urinary hFSH for stimulating follicular development in women undergoing IVF-ET. DESIGN Multicenter, prospective, randomized, open, parallel group, clinical study. SETTING Eight European academic IVF units and one private IVF unit. PATIENTS Infertile female patients aged 18 to 38 years suffering from tubal disease, mild endometriosis, or unexplained infertility. INTERVENTIONS Pretreatment with buserelin acetate was followed by recombinant or urinary hFSH treatment started at an initial dose of 225 IU FSH/d. Dose adjustment was allowed after 5 days of FSH. After administration of hCG, a standard IVF-ET procedure was performed. MAIN OUTCOME MEASURES Follicular development, oocyte retrieval, fertilized oocytes, duration and dose of FSH, and pregnancy. The hypothesis formulated before the study was that no difference was expected between the two FSH preparations. RESULTS Sixty patients were treated with recombinant hFSH and 63 with urinary hFSH. The mean number (+/- SD) of growing follicles (mean diameter > 10 mm) was 10.3 +/- 4.9 and 11.2 +/- 5.2, of follicles (mean diameter > 14 mm) was 7.8 +/- 3.6 and 9.2 +/- 4.5, of retrieved oocytes was 9.3 +/- 5.0 and 10.7 +/- 5.3, and of fertilized oocytes was 5.6 +/- 3.8 and 6.5 +/- 4.3, for recombinant and urinary hFSH, respectively. The duration of FSH treatment was 9.9 +/- 2.3 and 9.4 +/- 1.8 days and the average total dose was 2270 +/- 714 and 2095 +/- 591 IU of FSH, for recombinant and urinary hFSH, respectively. Thirteen pregnancies were recorded in the recombinant hFSH group and 11 in the urinary hFSH group. Nine patients delivered 13 live infants in the recombinant hFSH group and eight delivered 13 live infants in the urinary hFSH group. In terms of safety, no difference was recorded between the groups and no anti-FSH antibodies were found in any of the patients. CONCLUSIONS This clinical study shows that recombinant hFSH is as safe and effective as urinary hFSH in stimulating ovarian follicular development.

Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden

OBJECTIVE To study the association between hormonal infertility treatment and ovarian neoplasia. DESIGN Historical cohort study. SETTING Three university hospitals in Sweden. PATIENT(S) A total of 2,768 women assessed and treated for infertility and infertility-associated disorders between 1961 and 1975. INTERVENTION(S) Exposed women received clomiphene citrate and/or gonadotropins. MAIN OUTCOME MEASURE(S) Incidence of ovarian neoplasia. RESULT(S) No overall excess risk of invasive ovarian cancer emerged compared with the general population. In women with gonadotropin treatment for non-ovulatory disorders, the risk was elevated (standardized incidence ratio [SIR] = 5.89; 95% confidence interval [CI] 1.91-13.75); four of the five cases reported hCG treatment only, rendering the biological plausibility uncertain. Multivariate analysis within the cohort indicated that treatment with gonadotropins only was associated with an increased risk of invasive cancer (relative risk = 5.28; 95% CI 1.70-16.47). For borderline tumors, a more than threefold overall increase of tumors (SIR = 3.61; 95% CI 1.45-7.44) was noted; women exposed to clomiphene because of ovulatory disorders showed the highest risk (SIR = 7.47; 95% CI 1.54-21.83). CONCLUSION(S) Our findings of increased risk of ovarian cancer after gonadotropins and of borderline tumors after clomiphene treatment need to be interpreted with caution. However, concern is raised, and further research on the long-term safety particularly of modern hormonal infertility treatment in IVF programs is warranted.

Regression of a Prolactin-Secreting Pituitary Tumor During Long-Term Treatment with Bromocriptine

A nulliparous woman with 12 years of amenorrhea, galactorrhea, and hyperprolactinemia and radiologic evidence of a pituitary macroadenoma was treated with large doses of bromocriptine. During treatment the greatly increased prolactin levels normalized and ovulatory menstrual cycles were regained after 48 weeks of treatment. A transsphenoidal surgical exploration of the pituitary fossa was performed after 27 months of treatment. The findings at surgery suggested that regression of the pituitary adenoma had occurred during the prolonged treatment with bromocriptine. After discontinuation of the therapy, the patient continued to ovulate and subsequently conceived.

MENSTRUAL FUNCTION AND SERUM PROLACTIN LEVELS AFTER LONG-TERM BROMOCRIPTINE TREATMENT OF HYPERPROLACTINAEMIC AMENORRHOEA

Long‐term bromocriptine treatment was discontinued in thirty‐seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty‐seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but only three were normoprolactinaemic 3 months after stopping treatment. Two of the seven women had evidence of pituitary tumour regression. After the discontinuation they had nearly normal prolactin levels but during 2 years of follow up the serum prolactin levels slowly increased. In the twenty‐seven women with pre treatment prolactin levels below 100 μg/l there was no difference between the prolactin levels before starting and 1 month after stopping treatment, while the women with pretreatment prolactin levels above 100 μ/l had lower levels after therapy. Bromocriptine treatment seldom results in permanent cure of hyperprolactinaemic amenorrhoea.

Addition of gonadotrophin‐releasing hormone agonist and/or two inseminations with husband's sperm do not improve the pregnancy rate in superovulated cycles

Background. A prospective randomized study was performed to evaluate the addition of a gonadotropin releasing hormone agonist (GnRH‐a) during treatment with human menopausal gonadotropins (hMG) in cycles with artificial inseminations with husbands washed sperm (AIH). We also compared the pregnancy rate per cycle after one versus two AIHs.

Rapid Regression of Pituitary Tumours during Bromocriptine Treatment of Women with Hyperprolactinaemia

Four hyperprolactinaemic women with large pituitary adenomas with suprasellar extension were given primary tumour therapy with bromocriptine. The treatment resulted in rapid tumour regression in all the women, as verified by repeated computerized tomography (CT) scans. Pronounced visual field defects were present in three of the four women before treatment. All of them had marked improvement of vision within a few days after the initiation of bromocriptine therapy and they regained normal or nearly normal visual fields during the treatment. The raised serum prolactin concentrations decreased to normal levels in all the women. Thus, medical treatment with bromocriptine can induce rapid tumour regression in patients with hyperprolactinaemia and large pituitary tumours.

The Importance of Human Chorionic Gonadotropin Support of the Corpus Luteum during Human Gonadotropin Therapy in Women with Anovulatory Infertility

One hundred ten women with anovulatory infertility (World Health Organization [WHO] group I n = 50, WHO group II n = 60) were given 341 treatment courses with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Additional hCG was given as single or repeated injections during the luteal phase in 205 ovulatory cycles. In WHO group I, the incidence of luteal phase defects was lower and the pregnancy rate higher in cycles with extra hCG administration during the luteal phase than in cycles with no extra hCG. In WHO group II, there was no such difference after supplemental hCG. The abortion rate was the same after cycles with or without extra hCG administration. It is suggested that during ovulation induction with hMG/hCG in anovulatory women with no evidence of endogenous estrogen activity, the luteal phase should be supplemented with additional hCG.