Machelle M. Seibel

Reproductive endocrine disorders in women with partial seizures of temporal lobe origin

Of 50 consecutive women with partial seizures of temporal lobe origin (temporal lobe epilepsy [TLE]) evaluated for reproductive dysfunction, 28 had menstrual problems. Of those, 19 had reproductive endocrine disorders. Polycystic ovarian syndrome and hypogonadotropic hypogonadism occurred significantly more often in women with TLE than in the general female population. Polycystic ovarian syndrome was associated with predominantly left-sided lateralization of interictal epileptic discharges; hypogonadotropic hypogonadism was more commonly found with right-sided discharges. Hyposexuality occurred more often in women with predominantly right-sided interictal epileptic discharges and was associated with low serum luteinizing hormone levels. There are several possible interpretations: epileptic discharges in medial temporal limbic structures may disrupt hypothalamic regulation of pituitary gonadotropin secretion; anovulatory cycles of reproductive endocrine disorders may promote the development of epileptic discharges; and TLE and some associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of the brain and the reproductive system.

Emotional aspects of infertility

The psychologic aspects of infertility in men and women are reviewed, neuroendocrinologic factors thought to affect reproduction physiologically are described, and awareness of the stresses that infertility places on a couples relationship is encouraged. Studies have found infertile women to be more neurotic, dependent, and anxious than fertile women, experiencing conflict over their femininity and fear associated with reproduction. In contrast to these reports, a double blind study could not determine the difference in the psychologic makeup of women who were infertile because of demonstrated somatic causes and those women in whom no somatic cause could be found and who were considered infertile on an emotional etiologic basis. Other studies have similarly come to negative conclusions regarding the relationship between psychologic factors and infertility. The 1st set of studies failed to consider the stress that infertility itself places on the couple. Emotional factors may negatively affect fertility in the male. Up to 10% of infertile males have had improvement in their semen analysis after cessation of all treatment for a prolonged period of time. The concept that emotional stress might lead to oligospermia was further supported in a report describing testicular biopsies obtained from men awaiting sentencing after raping and impregnating women. A more obvious effect of the emotional stress infertility places on the male is the occurrence of impotence. It has been estimated that up to 10% of infertilty may be partially or completely explained on the basis of male sexual dysfunction. The gradual unraveling of the complexities of neuroendocrinology have permitted increased understanding of the role that stress might play in infertility. Catecholamines, prolactin, adrenal steroids, endorphins, and serotonin all affect ovulation and in turn are all affected by stress. Such stress might result from infertility or habitual abortion. Infertility is frequently perceived by the couple as an enormous emotional strain, and counseling may prove helpful as a part of the initial infertility evaluation, an adjunctive measure during treatment, or a final measure to help patients cope with acceptance of their infertility problem. Although statistical evidence is overwhelmingly against the relationship of adoption and subsequent conception, it does appear that a small percentage of patients do achieve pregnancy following adoption. Possibly this can be explained by a reduction in stress, and subsequently, alterations in the neuroendocrinologic characteristics of the infertile couple.

The prevalence and predictability of depression in infertile women.

OBJECTIVE To determine the prevalence, severity, and predictability of depression in infertile women compared with a control sample of healthy women. DESIGN Subjects were assessed while waiting to see their physician: infertility patients before a visit with an infertility specialist and control subjects before seeing either a gynecologist or internist for a routine gynecological examination. Subjects completed a demographic form and two depression scales. SETTING A group infertility practice affiliated with an academic medical center, a hospital-based gynecology practice, and a health maintenance organization internal medicine clinic. PARTICIPANTS 338 infertile women and 39 healthy women. INTERVENTIONS None. MAIN OUTCOME MEASURES The Beck Depression Inventory and the Center for Epidemiological Studies Depression Scale. RESULTS The infertile women had significantly higher depression scores and twice the prevalence of depression than the controls; women with a 2- to 3-year history of infertility had significantly higher depression scores compared with women with infertility durations of < 1 year or > 6 years; women with an identified causative factor for their infertility had significantly higher depression scores than women with unexplained or undiagnosed infertility. CONCLUSIONS Depressive symptoms are common in infertile women. Psychological interventions aimed at reducing depressive symptoms need to be implemented, especially for women with a definitive diagnosis and for those with durations of 2 to 3 years of infertility.

Tubal Infertility and the Intrauterine Device

To study the association between intrauterine devices (IUDs) and pelvic inflammatory disease, we compared contraceptive histories in 4185 while women--283 nulliparous women with primary tubal infertility, 69 women with secondary tubal infertility, and 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with IUD use was calculated by means of multivariate logistic regression to control for confounding factors, including region, year of menarche, religion, education, smoking, and reported number of sexual partners. The adjusted risk of primary tubal infertility associated with any IUD use before a first live birth was 2.0 (95 per cent confidence limits, 1.5 to 2.6) relative to nonuse. Users of the Dalkon Shield had an adjusted risk of 3.3 (1.7 to 6.1), users of the Lippes Loop or Saf-T-Coil had a risk of 2.9 (1.7 to 5.2), and users of copper IUDs had a risk of 1.6 (1.1 to 2.4). Women who reported having only one sexual partner had no increased risk of primary tubal infertility associated with IUD use. The adjusted risk of secondary tubal infertility associated with use of a copper IUD after a first live birth was not statistically significant (1.5; 95 per cent confidence limits, 0.8 to 3.0), whereas the risk from similar use of noncopper devices was significant (2.8; 1.3 to 5.9). We conclude that tubal infertility is associated with IUD use, but less so with copper IUDs.

The Mind/Body Program for Infertility: a new behavioral treatment approach for women with infertility

There is increasing evidence that a behavioral treatment approach might be efficacious in the treatment of the emotional aspects of infertility and may lead to increased conception rates. The first 54 women to complete a behavioral treatment program based on the elicitation of the relaxation response showed statistically significant decreases in anxiety, depression, and fatigue as well as increases in vigor. In addition, 34% of these women became pregnant within 6 months of completing the program. These findings established a role for stress reduction in the long-term treatment of infertility. They further suggest that behavioral treatment should be considered for couples with infertility before or in conjunction with reproductive technologies such as intrauterine insemination and gamete intrafallopian transfer.

The impact of embryo quality and quantity on implantation and the establishment of viable pregnancies

The role of cleavage rates, number of embryos transferred, and some other variables in pregnancy outcome in 222 human embryo transfers was studied. Pregnancy rates were significantly higher in a group of 117 patients receiving at least one embryo that had reached the four-cell stage at 40 hr postinsemination (26% total pregnancies/transfer and 18% ongoing pregnancies/transfer) than in the 105 patients receiving embryos developing at a slower rate (7% total pregnancies/transfer and 2% ongoing pregnancies/transfer). Of the 23 ongoing or term pregnancies produced, 21 came from transfers of at least one embryo that had reached four-cell stage by 40 hr postinsemination. Pregnancy rates were unaffected in either the fast-cleaving or the slower-cleaving embryos by culturing in vitro for an additional 24 hr. The presence of anucleate cell fragments also had no effect on pregnancy rates. Pregnancy rates increased progressively with the transfer of more embryos per transfer. These results suggest that procedures to improve ovulation induction and in vitro embryo culture technique may better the success of in vitro fertilization by providing a high number of rapidly cleaving embryos for transfer.

Altered pulsatile secretion of luteinizing hormone in women with epilepsy

Menstrual disorders and infertility are common among women with epilepsy of temporal lobe origin (TLE). Reproductive endocrine disorders may be the cause. Polycystic ovarian syndrome (PCO) and hypothalamic amenorrhea (hypogonadotropic hypogonadism, HH), in particular, are significantly overrepresented and attributable to hypothalamic dysfunction. We therefore compared the hypothalamic function of 14 women with clinically and electrographically documented TLE with that of eight age-matched normal controls by determining the interictal pulse frequency and amplitude of luteinizing hormone (LH) secretion. Serum for LH measurement was drawn every 15 minutes from 8 AM to 4 PM in both groups. LH pulse frequency values were significantly more variable (p < 0.05) and lower (p < 0.05) among women with TLE than among controls. Women with left temporal EEG foci showed a trend toward higher pulse frequencies compared to women with right foci (p = 0.05 to 0.10). Among five women with reproductive endocrine disorders, the three with PCO had left-sided foci and average LH pulse frequency two times higher than that of the two women with HH, who had right-sided foci. Eight reproductively normal, medically treated women with TLE had significantly lower LH pulse frequencies than did the one reproductively normal, untreated woman with TLE (p < 0.05) and the eight normal controls (p < 0.001). These findings suggest that LH pulse frequencies in women with TLE may be influenced by the laterality of the epileptic focus, the reproductive endocrine status, and the use of antiseizure medications.

The effectiveness of danazol on subsequent fertility in minimal endometriosis

Sixty-five patients with minimal endometriosis were studied for the purpose of prospectively comparing conservative medical management in the form of danazol with no therapy in the treatment of this disease. After completion of the basic infertility evaluation and correction of additional factors affecting fertility, a diagnostic laparoscopy, dilatation and curettage (D and C), and tubal lavage were performed. A randomly selected cord determined whether the patient received no treatment for 6 months or danazol for 6 months followed by no treatment for 6 months. The dosage of danazol was 800 mg daily for the first 2 months, 600 mg daily for the next 2 months, and 400 mg daily for the final 2 months. The mean age of both the danazol-treated group and the group that received no danazol was 31 years. Conception occurred in 30% of the danazol-treated patients and 50% of the untreated patients. These results suggest that infertile patients with minimal endometriosis should be given an opportunity to conceive after laparoscopy, D and C, and tubal lavage. This would seem particularly true in older patients where a 6-month delay in permitting attempts at conception represents a significant interval of time.

Temporal lobe epilepsy An extrahypothalamic pathogenesis for polycystic ovarian syndrome

In a random sample of 20 women with temporal lobe epilepsy (complex partial seizures, CPS), we found 5 women with the polycystic ovarian syndrome. This finding in a small sample suggests a fivefold overrepresentation of polycystic ovarian syndrome among women with CPS. Clinical and experimental data support the notion that CPS and polycystic ovarian syndrome either favor a mutual development or are parallel effects of a common pathogenesis.

Psychological improvement in infertile women after behavioral treatment: a replication * †

OBJECTIVE To replicate previously reported psychological improvements in infertile women attending a group behavioral treatment program. DESIGN Psychological and demographic data were collected before entering and again upon completion of a behavioral medicine program on a second cohort of patients. SETTING The program was offered in the Division of Behavioral Medicine, an outpatient clinic of the Department of Medicine at New England Deaconess Hospital. All patients were receiving care from infertility specialists not affiliated with this hospital. PATIENTS Fifty two self-referred women receiving medical treatment for infertility attended the program. INTERVENTION A 10-week group behavioral treatment program. MAIN OUTCOME MEASURES Three validated psychological instruments. RESULTS Psychological improvement was statistically significant (Profile of Mood States Tension/Anxiety: P less than 0.0001; Depression/Dejection: P less than 0.0122; Vigor/Activity: P less than 0.0431; Confusion/Bewilderment: P less than 0.0057; Spielberger Anger Expression: P less than 0.0013; Spielberger State Anxiety: P less than 0.0037, and Trait Anxiety: P less than 0.0001). CONCLUSIONS Behavioral treatment is associated with significant decreases in negative psychological symptoms.