I.D. Cooke

The septate uterus: a review of management and reproductive outcome

OBJECTIVE To review the literature on the diagnosis, prevalence, and treatment of the septate uterus, with special reference to hysteroscopic metroplasty and its effect on reproductive outcome. DESIGN Pertinent studies were identified through a computer MEDLINE search. References of selected articles were hand-searched for additional citations. RESULT(S) Reliable diagnosis of the septate uterus depends on accurate assessment of the uterine fundal contour. At present, the combined use of laparoscopy and hysteroscopy is the gold standard for diagnosis, although recent reports of two-dimensional, transvaginal, contrast ultrasound and of three-dimensional ultrasound appear promising. The prevalence of the septate uterus is increased in women with repeated pregnancy loss. A metaanalysis of published retrospective data comparing pregnancy outcome before and after hysteroscopic septoplasty indicated a marked improvement after surgery. CONCLUSION(S) The hysteroscopic approach to treatment, with its simplicity, minimal postoperative sequelae, and improved reproductive outcome, has enabled a more liberalized approach to treatment that is now being extended to include not only patients with recurrent pregnancy loss and premature labor but also patients with infertility, especially if IVF is being contemplated.

A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility

OBJECTIVE To determine the effectiveness of the in vivo administration of vitamin E as treatment for reactive oxygen species-associated male infertility. SETTING University-based center for reproductive medicine. DESIGN Double-blind randomized placebo cross-over controlled trial. PATIENTS, PARTICIPANTS Thirty healthy men with high levels of reactive oxygen species generation in semen and a normal female partner. INTERVENTIONS Patients were allocated to two groups according to the blinded randomization. Each patient received either 600 mg/d of vitamin E (Ephynal, 300 mg tablets; F. Hoffman-La Roche Ltd., Basle, Switzerland) (order A) or identical placebo tablets (order B) for 3 months. Then after a 1-month wash-out period the patients were crossed-over to the other treatment. MAIN OUTCOME MEASURES Improvement in the in vitro function of the spermatozoa measured by conventional semen analysis, computerized motility assessment, determination of reactive oxygen species generation, binding to the zona pellucida of the unfertilized human oocyte in a competitive zona binding assay, development of hyperactivated motility (both spontaneous and in the presence of 20% of the natural agonist, human follicular fluid) and pregnancy. RESULTS Rise in the blood serum vitamin E levels after treatment accompanied by improvement in one of the sperm function tests: the zona binding assay. The zona binding ratio for order A improved from 0.2 (range 0 to 0.5) before treatment to 0.5 (range 0.1 to 1.0) after treatment, the corresponding values for order B were 0.2 (range 0 to 1.0) before treatment and 0.3 (range 0.1 to 0.7) after treatment. CONCLUSION Oral administration of vitamin E significantly improves the in vitro function of human spermatozoa as assessed by the zona binding test.

The role of T-helper cytokines in human reproduction

OBJECTIVE To explore the role of maternal periimplantation endometrial T-helper-1 (TH-1) and T-helper-2 (TH-2) cytokines in the success or failure of human reproduction and their relation to the endocrine system and subsequent pregnancy outcome. DESIGN Controlled, prospective study. SETTING A tertiary care hospital with a university-based reproductive medicine clinic. PATIENT(S) Healthy women and women with recurrent miscarriage who had no history of infertility or autoimmune disease. INTERVENTION(S) Measurement of qualitative cytokine expression by RT-PCR and quantitative by ELISA, also hormone levels and pregnancy outcome. MAIN OUTCOME MEASURE(S) Expression of TH-1 and TH-2 cytokines and correlation with hormone levels and subsequent pregnancy outcome. RESULT(S) Levels of TH-1 cytokines were significantly greater and higher in women with recurrent miscarriage compared with controls, whereas levels of TH-2 cytokine interleukin-6 were significantly lower in women with recurrent miscarriage than in controls. There was no correlation between cytokine expression and serum hormone levels, and periimplantation cytokine levels were not predictive of subsequent pregnancy outcome in women with recurrent miscarriage. CONCLUSION(S) This study demonstrated in vivo that women with recurrent miscarriage exhibit primarily TH-1 cytokines, whereas healthy women exhibit decreased TH-1 cytokines and increased TH-2 cytokines. This suggests a potential role for a dichotomous T-helper response in the mediation of subsequent reproductive events. This maternal T-helper response appears to operate independently of hormonal factors in influencing the success or failure of human reproduction, as no correlation was evident between serum hormone levels and cytokine levels. An attempt to use periimplantation TH-1 and TH-2 cytokine profiles as a predictor of subsequent pregnancy outcome (live birth or no live birth) was limited by the small number of patients studied.

Progressive changes in LH and FSH and LH: FSH ratio in women throughout reproductive life

Gonadotropin secretion during the post-menopausal period is considerably higher than during the reproductive years. In this study, we present evidence that changes in the hypothalamic-pituitary-ovarian unit occur over a period of years before the onset of menstrual irregularity which heralds the menopause. FSH and LH were measured in blood samples taken on 6 days during the mid-follicular phase from 127 regularly cycling women aged between 23 and 49 yr. The women aged 23-30 yr were taken as the control group and the remainder were grouped in 2-yr age bands. A significant increase in FSH underwent a further increase in the oldest group (48-49 yr) in whom LH also became significantly elevated. The difference in the timing of the change in FSH and LH concentrations was related not only to chronological age but also to the number of years before the menopause. The increase in FSH occurred 5-6 yr pre-menopause, that in LH not until 3-4 yr before the cessation of menstruation. It is concluded that an early sign of the aging of the reproductive mechanism can be detected in women who are having normal ovulatory cycles. The regulation of FSH and LH secretion appears to be sufficiently independent to permit the observed differences in the age of onset of these premenopausal increases.

An assessment of continuous fetal heart rate monitoring in labor

Intrapartum continuous fetal heart rate monitoring has been routinely performed at the Jessop Hospital for Women for some years. However, no controlled trials had ever been performed to show its advantages over intermittent auscultation in low-risk patients. A prospective randomized study of 504 patients compared continuous fetal heart rate monitoring with intermittent auscultation. There was no significant difference between the two groups in neonatal deaths, Apgar scores, maternal and neonatal morbidity, and cord blood gases. The cesarean section rate was significantly increased (p less than 0.05) in the monitored patients but this did not seem attributable to fetal monitoring. No beneficial or deleterious effects of continuous fetal heart rate monitoring in labor were shown.

The impact of infertility on psychological functioning

To explore the impact of infertility on psychological functioning 130 couples presenting with primary infertility were assessed at their initial visit to an infertility clinic. Of these, 116 couples were assessed on a second occasion some 7-9 months later when in most cases the medical tests were complete. Measures of personality, psychopathology, perceived social support, sex role identity and marital state were obtained from both partners. The set was subsequently divided into five subgroups on the basis of the diagnosis made or the outcome (female cause, male cause, female and male cause, unexplained and pregnant). The results show little evidence of psychopathology in the sample, depression scores remained low throughout the period of investigation. The results also indicated stable marital relationships. Scores on tests of anxiety and psychiatric morbidity declined between the first and second assessment except in the case of men who were diagnosed with a fertility problem. The implications of these findings are discussed in the increased use of donor insemination which circumvents rather than treats the problem of male infertility.

Prognostic significance of computerized motility analysis for in vivo fertility

OBJECTIVE To determine the predictive value of quantitative motility characteristics produced by the Hamilton Thorn Motility (HTM) Analyzer (Hamilton Thorn Research, Beverley, MA) for in vivo conception. DESIGN A prospective analysis of 222 couples attending a regional infertility clinic. The measurements were made on a semen sample, and the presence or absence of a treatment-independent conception up to 22 months later was determined. The semen variables were then correlated to conception. SETTING University based center for reproductive medicine. PATIENTS, PARTICIPANTS The presence or absence of an in vivo conception was recorded in 222 couples in whom the influence on fertility of the female partner was minimized, i.e., normal in terms of history and examination, a regular menstrual cycle, ovulatory (midluteal serum P > 18 nmol/L [5.6 ng/mL]), and the outcome of the hysterosalpingogram was normal. The median follow-up time was 13 months (range, 5 to 22 months). INTERVENTIONS None. MAIN OUTCOME MEASURE Pregnancy. RESULTS A number of variables were significantly related to time to conception. When a forward stepwise analysis was performed, the total number of spermatozoa was selected on the first step, and average path velocity was selected on the second step. No other variables were selected. The final variables consisted of the total number of spermatozoa and average path velocity. CONCLUSION The measurement of quantitative motility and sperm number using a HTM Analyser is of clinical value.

Hypothalamic‐pituitary ageing: progressive increase in FSH and LH concentrations throughout the reproductive life in regularly menstruating women

OBJECTIVE Reproductive ageing is associated with reduced fertility and endocrine changes that become more pronounced during the perimenopausal period. We aimed to assess changes in gonadotrophin concentrations and the onset of these changes during the reproductive life prior to the perimenopause.

Factors affecting the outcome of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility

Objective To describe and analyse the factors affecting the pregnancy rate of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility.

Successful treatment of asymptomatic endometriosis: Does it benefit infertile women?

The relation between asymptomatic endometriosis and infertility was investigated in a randomised double blind placebo controlled trial of the impact of treating the endometriosis with gestrinone. The 12 month cumulative conception rate in those patients treated with gestrinone was 25% (5/20) and in those given placebo 24% (4/17). These same patients were divided into those in whom no visible endometriosis was present at the second laparoscopy and those in whom residual disease was present and the 12 month cumulative conception rates were 25% (4/16) and 30% (6/20) respectively. None of these rates differed significantly, and they compared with a rate of 23% (6/26) in a control group of patients with unexplained infertility. Those patients in whom the disease was eliminated did not return to normal fertility, though all other causes of infertility were excluded. This study failed to show any impact of treatment or the absence or presence of asymptomatic endometriosis on future fertility compared with patients with unexplained infertility. The findings therefore question any causal role of the disease in infertility.