Ottar Lunde

Obstetric outcome in singleton pregnancies after assisted reproduction

Objective To compare the obstetric outcome of singleton pregnancies after various procedures of assisted reproduction with a control group. Methods Maternal and perinatal outcome in 355 assisted-reproduction singleton pregnancies (study group) with a duration of 140 days or more were compared retrospectively with a control group matched for age and parity. All assisted-reproduction pregnancies resulted from treatment in one university hospital, and all control subjects delivered in the obstetric department of the same hospital. The controls consisted of 643 women, also with singleton pregnancies, who were matched for age and parity. Results In the study group, the frequencies of pregnancy-induced hypertension and placenta previa were increased. More patients in the study group were delivered by elective cesarean. Pregnancies after assisted reproduction were of shorter duration, with an increased incidence of preterm birth. Infants in the study group had a lower mean birth weight than did those in the control group and were more frequently referred to a neonatal care unit. Conclusion Singleton pregnancies resulting from assisted reproduction represent obstetric risk cases, and the patients should be offered special attention during the pregnancy, which will probably be their only one.

Familial clustering in the polycystic ovarian syndrome

To assess the degree of familial clustering and the mode of inheritance of the polycystic ovarian syndrome (PCO), the prevalence of PCO-related symptoms among first- and second-degree relatives of 132 PCO patients and 71 controls was studied using questionnaire data. 19.7% of male first-degree relatives of PCO patients were reported to have early baldness or excessive hairiness, as opposed to 6.5% of relatives of controls. For female first-degree relatives, the percentages for PCO-related symptoms were 31.4 and 3.2, respectively, in the two groups. In a subgroup of 52 families of PCO patients where one of the parents was reported to have symptoms, 35% of brothers and 58% of sisters had symptoms. Although autosomal dominant inheritance could be excluded as an explanation for PCO in the whole data set, the findings were consistent with this mode of inheritance for a sizeable fraction of families. X-linked dominant inheritance of PCO could be discarded.

Prediction of response to controlled ovarian hyperstimulation: a comparison of basal and clomiphene citrate-stimulated follicle-stimulating hormone levels

OBJECTIVE To test the ovarian reserve in a high-risk population before controlled ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN A prospective study comparing the outcome of a clomiphene citrate (CC) challenge test to the outcome of subsequent IVF cycles. SETTING Unit for assisted reproductive technology in a university hospital. PATIENTS, PARTICIPANTS Ninety-one infertile women with an age of 35 years or more, who had previous ovarian surgery or who had been diagnosed with ovarian endometriosis. MAIN OUTCOME MEASURE Relate follicle-stimulating hormone (FSH) levels before and after CC to frequency of cancellation of an IVF cycle because of a poor follicular response. RESULTS Twenty-one patients had elevated basal levels of FSH. Thirty-seven patients, including 20 with high basal levels, showed an excessive FSH response to CC with an FSH level after CC above the 95% confidence limit. Clomiphene citrate-stimulated FSH levels correlated better than basal levels with response to controlled ovarian hyperstimulation. An excessive FSH response to CC predicted a poor response outcome of subsequent controlled ovarian hyperstimulation for IVF with 85% accuracy. CONCLUSION Follicle-stimulating hormone response to CC predicts subsequent follicular response to controlled ovarian hyperstimulation.

Infertility and chlamydial infection

The prevalence of humoral IgG and IgM antibodies to Chlamydia trachomatis was determined in 105 infertile women who underwent laparascopy and/or laparatomy, and 90 pregnant women without any known fertility problems (control group). For chlamydial culture, cervical and urethral specimens were collected both from the infertile and the pregnant women, whereas specimens from the fallopian tubes were collected from the infertile women only. Among infertile subjects with abnormal fallopian tube findings, the prevalence of IgG as well as IgM antibodies to C. trachomatis was significantly higher than in the control group ( P ≤0.001). Similar statistically significant differences in antichlamydial geometric mean titer (GMT) also were observed in sera from infertile subjects with fallopian tube abnormalities and the controls. The chlamydial isolation rate from lower genital samples was low both among the infertile and pregnant women. All tubal samples were culture negative. The present study indicates a close connection between infertility of tubal etiology and an immune response to C. trachomatis . The possibility of active or recent chlamydial activity in at least some of these infertile subjects is discussed.

Ovulation induction with low-dose follicle-stimulating hormone in women with the polycystic ovary syndrome

Fifty infertile women with the polycystic ovary syndrome (PCOS) were treated for 66 cycles with low‐dose FSH stimulation starting with 75 IU FSH for two weeks before eventual stepwise increases in the gonadotropin dose occurred. An unifollicular response was observed in 35 (53%) cycles and in 20 (30%) cycles there were two‐three mature follicles. A multifollicular response (>3 mature follicles) resulted in 11 (17%) cycles. One of the 66 cycles was complicated with the ovarian hyperstimulation syndrome. Twelve (22%) pregnancies were obtained following 55 completed cycles. All ongoing pregnancies were singleton gestations. The obese PCOS women required a longer period of stimulation and a higher amount of gonadotropin to achieve follicular maturation. However, there was no difference in cycle cancellation or pregnancy rate between obese and non‐obese PCOS women. Thus low‐dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate in PCOS women.

Polycystic ovary syndrome: a follow-up study on diabetes mellitus, cardiovascular disease and malignancy 15-25 years after ovarian wedge resection.

The aim of the present study was to examine the occurrence of possibly associated diseases in 149 women with polycystic ovary syndrome (PCOS) 15–25 years after ovarian wedge resection. Diabetes mellitus was the only associated disease which showed a significantly increased occurrence. No significant change in cancers specific for the female gender was seen. Likewise, the relative risk of cardiovascular disease was not affected. However, the power of the statistical test was low. This long-term study indicates increased risk of diabetes mellitus in PCOS patients. The study group is too small to give any conclusions about other possibly associated diseases. Family histories, however, revealed that associated diseases are related to genetic disposition rather than to PCOS per se.

Mitotically active cellular luteinized thecoma of the ovary and luteinized thecomatosis associated with sclerosing peritonitis: case studies, comparison, and review of the literature.

In this study, we distinguish two clinical and pathological entities that are similarly named: luteinized thecoma and luteinized thecoma associated with sclerosing peritonitis. Ovarian luteinized thecoma lacks definitive criteria for malignancy. Based on our case study of a mitotically active neoplasm without nuclear atypia in which the patient was living and well 19 years after operation and comparison with prior studies of luteinized thecoma and the closely related entity of cellular fibroma, we propose presumptive criteria for malignancy for this rare neoplasm. Increased mitotic activity in luteinized thecoma without significant nuclear atypia is not an indication of malignant behavior, and such cases should therefore be referred to as mitotically active cellular luteinized thecoma. We also contrast neoplasms in the luteinized thecoma category with the entity originally reported as luteinized thecoma associated with sclerosing peritonitis. In the latter, the ovarian stromal proliferations are typically bilateral, can have an exceedingly high mitotic rate as was seen in our illustrative case, often incorporate non-neoplastic ovarian structures at their periphery, and are responsive to medical therapy. In our patient with sclerosing peritonitis, both the ovarian masses and peritoneal sclerosis underwent complete regression following treatment with gonadotropin-releasing hormone agonist and high doses of steroids, and an ovarian biopsy taken 2 months after therapy showed a histologically normal ovary. The patient subsequently became pregnant and delivered a normal infant. This is, to our knowledge, the first case of successful medically conservative treatment of a young patient with this entity that led to complete relief of symptoms and allowed preservation of fertility. Because recent observations support the non-neoplastic nature of the ovarian stromal proliferations, we advocate use of the previously proposed term luteinized thecomatosis associated with sclerosing peritonitis for this entity.

Ovarian Morphology in Patients with Polycystic Ovaries and in an Age-Matched Reference Material

The ovarian morphology in 149 patients with the clinical syndrome of polycystic ovaries (group I) is described. The ovaries from 10 age-matched women (group II) with no signs of ovarian disorder were investigated as a reference material. The number of cysts documented for group I was twice that of the reference group and the ovarian volume three times that of the normals. No significant difference in follicle number was seen between the two groups. The tunica albuginea was thicker in group I with more pronounced atretic changes. The duration of symptoms for group I correlated significantly with body mass index, thickening of tunica, degree of stromal hyperplasia and the calculated means of ovarian volume. A correlation was also seen between ovarian volume, degree of follicular atresia and stromal hyperplasia, as well as between the thickness of the tunica albuginea, number of follicles and degree of follicular atresia.

Heterotopic pregnancy following in vitro fertilization

We report 4 cases of heterotopic pregnancy following in vitro fertilization. AH 4 patients were treated by surgical removal of the ectopic pregnancy products. In 3 patients, the intra‐uterine fetus was alive prior to surgery. Two of the 3 gave birth to a healthy baby while the third pregnancy has progressed uneventfully for 12 weeks since the operation.

Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome

The study focuses upon the problems associated with androgen hyperfunction, with particular emphasis on the polycystic ovarian syndrome. The objective of the investigation was to shed light on the etiology and diagnosis of and therapy for this endocrine dysfunction. Gross sclerocystic changes in the human ovary have been reported in the literature since the middle of the 19th century. Before the turn of the century, oophorectomy as well as partial resection of the ovaries were widely used therapeutic procedures. In 1935 Stein & Leventhal described the clinical syndrome associated with polycystic ovaries; chronic anovulation with infertility and androgen hyperfunction are the chief elements of this condition and for many years it was called the Stein-Leventhal syndrome. It proved, however, to be more heterogeneous than was initially assumed and the description polycystic ovarian syndrome is now preferred. Decades of endocrinologic research have elucidated some of the mechanisms leading to the condition but the lack of clear definitions has hindered clinical research. The first paper in the thesis has established a normal material for hair growth in Norwegian women. In the second, a scoring system was developed by which we were able to distinguish hirsutism from normal hair growth in 97-98% of the cases studied. This is of great clinical importance, as it not only selects those cases where increased hair growth might be an early sign of underlying disease, but also reassures those patients whose hair growth falls within the variation of the normal population. The third paper describes the first comparative study of the effect of the two most widely used anti-androgens on hair growth. The result obtained provide a valuable guide in the choice of therapy for hirsutism. The fourth paper delineates a case of androgenproducing ovarian tumour. Usually this condition is accompanied by an excessive and irreversible defeminization, but our patient may represent one of the few cases where progressive hirsutism can disappear after treatment. In the fifth paper, ovarian morphology in 149 patients with polycystic ovarian syndrome has been compared with an age-matched reference material. The results contradict the significance of ovarian morphology as a diagnostic criterion, but establish atresia as the parameter which distinguishes conclusively between the two groups, with a significant difference and n o overlap. It would therefore appear timely and pertinent to rename this ovarian disorder “atretic ovarian syndrome”. The sixth paper describes the therapeutical effectiveness of ovarian wedge resection. However, similar but less invasive techniques are nowadays recommended. In article number seven, genetic mechanisms have been evaluated in the polycystic ovarian syndrome. 132 patients and their families have been compared with a reference group of 71 families, with special regard to autosomal dominant inheritance. The most quoted study on this issue, where 18 families were evaluated, concluded that autosomal dominant inheritance was the most probable cause. In the present study, autosomal dominant inheritance could be excluded as an explanation for polycystic ovarian