To study the effect of E2 and P on the epithelial cell cycle of normal human breast in vivo. Double-blind, randomized study. Topical application to the breast of a gel containing either a placebo, E2, P, or a combination of E2 and P, daily, during the 10 to 13 days preceding breast surgery. Forty premenopausal women undergoing breast surgery for the removal of a lump. MAIN OUTCOME MEASURES. Plasma and breast tissue concentrations of E2 and P. Epithelial cell cycle evaluated in normal breast tissue areas by counting mitoses and proliferating cell nuclear antigen immunostaining quantitative analyses. Increased E2 concentration increases the number of cycling epithelial cells. Increased P concentration significantly decreases the number of cycling epithelial cells. Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.
InfertilityClomiphene Citrate Side EffectsVisual DisturbanceFertility Drug Complications
To identify a distinctive constellation of persistent visual abnormalities secondary to treatment with clomiphene citrate. Description of the clinical findings in three patients with visual disturbance secondary to clomiphene treatment. A neuro-ophthalmology referral center. Three women aged 32 to 36 years treated for infertility with clomiphene for 4 to 15 months. All three patients experienced prolonged afterimages (palinopsia), shimmering of the peripheral field, and photophobia while undergoing treatment with clomiphene. The results of the neuro-ophthalmologic examination and electrophysiologic studies were normal in all three patients. Unlike previously reported cases, visual symptoms did not resolve on cessation of treatment. Patients remain symptomatic from 2 to 7 years after discontinuing treatment with the medication. Treatment with clomiphene can cause prolonged visual disturbance. Patients who develop such symptoms should be advised that continued administration may cause irreversible changes. Women with characteristic visual symptoms should be questioned about past use of clomiphene.
Lanzone A et al., 1995·The Journal of reproductive medicine
We investigated the impact of pregestationally elevated insulin plasma levels on glycemic control in pregnant women with polycystic ovary disease (PCOD). Twelve patients with PCOD who became pregnant within six months following evaluation of their metabolic status were the study subjects. Four were obese and six (two obese) had a hyperinsulinemic response to the oral glucose tolerance test (OGTT). They were tested with the OGTT at 28-30 weeks of gestation. We also tested 12 normal patients and 10 consecutive patients with gestational diabetes; all were at the same gestational age. Plasma levels of insulin and glucose were determined in the samples collected for a period of four hours after glucose load (100 g). All PCOD patients significantly increased their insulin secretion in pregnancy. The hyperinsulinemic PCOD patients developed gestational diabetes (two patients) and impaired gestational glucose tolerance (three patients). The area under the insulin curve was greater in PCOD patients than in control and gestational diabetes patients (P < .01). In spite of their large increase in insulin secretion observed during pregnancy, patients with PCOD may develop a derangement of glycemic control, probably related to their pregestational insulinemic status.
To investigate the role of transcervical tubal catheterization in diagnosis and treatment of proximal tubal obstruction associated with salpingitis isthmica nodosa. Retrospective case study. University hospital and outpatient radiology practice. Fifty-two women with proximal tubal obstruction associated with salpingitis isthmica nodosa. Selective salpingography and catheter recanalization using fluoroscopic guidance. The number of tubes visualized to the fimbria as a percentage of the tubes with proximal tubal obstruction on the initial hysterosalpingogram was determined as a measure of diagnostic efficacy. To evaluate the treatment potential of catheter recanalization, the patients were grouped according to tubal status at the conclusion of the procedure and subsequent pregnancies were evaluated. Forty-seven of 65 tubes (72%) with proximal tubal obstruction were recanalized successfully. Among the 19 women who were able to conceive only via a recanalized salpingitis isthmica nodosa tube, there were 6 live births (32%) and two tubal pregnancies (10%). Selective salpingography allows complete tubal diagnosis in almost three fourths of patients with proximal tubal obstruction and salpingitis isthmica nodosa. The radiographic diagnosis of salpingitis isthmica nodosa may be pressure dependent. Intrauterine pregnancies occur via recanalized salpingitis isthmica nodosa tubes, therefore catheter recanalization may be attempted before tubal microsurgery or IVF in patients with proximal tubal obstruction and associated salpingitis isthmica nodosa.
Nordic Adhesion Prevention Study Group, 1995·Fertil Steril
To evaluate the efficacy of Interceed as an adjuvant in the prevention of postoperative adhesion reformation to the ovary, fallopian tube, and fimbria when used together with microsurgical techniques. Prospective, randomized, multicenter, controlled clinical study. Normal human volunteers in an academic research environment. Sixty-six women suffering from infertility due at least in part to bilateral tubal disease with bilateral adhesions attached to ovaries, fallopian tubes, and fimbriae. Adhesiolysis bilaterly through laparotomy with microsurgical techniques, application of Interceed on one of the sides randomly assigned not known by the surgeon before application, follow-up laparoscopy 4 to 10 weeks postoperatively, with each patient serving as her own control. Adhesion severity scores at all sites and number of adhesion free organs after laparotomy and follow-up laparoscopy. When the initial scores registered at the operation for fertility were compared with those registered at the second-look laparoscopy, the results indicated that gentle microsurgical techniques resulted in a significant reduction of postoperative adhesions. Adnexa, which were covered with Interceed, had significantly lower adhesion scores than the control adnexa, representing an improvement of 39% compared with microsurgery alone (control) in reducing adhesion reformation scores. When combined with microsurgical techniques, Interceed reduced adhesion reformation scores by 70%. The number of ovaries, fallopian tubes, and fimbriae without adhesions at the time of second-look laparoscopy was significantly increased by approximately twofold when organs were covered with Interceed. In a prospective, randomized, multicenter, controlled clinical study using a protocol in which other adjuvants have been shown not to be efficacious, Interceed was shown to reduce significantly the incidence and severity of adhesion reformation to the ovary, fallopian tube, and fimbria after infertility surgery.
Myomectomy Adhesion Multicenter Study Group, 1995·Fertil Steril
To evaluate the effects of the expanded polytetrafluoroethylene barrier (PTFE), Gore-Tex Surgical Membrane, in reducing postmyomectomy adhesion formation. Multicenter randomized clinical trial. Twenty-seven women having myomectomy with at least two incisions on the uterine fundus and posterior uterine wall of similar length were enrolled in the study. At laparotomy, the two incision sites were randomly assigned to be covered with PTFE or were left uncovered. A second-look laparoscopy to evaluate adhesion formation and to lyse adhesions was done from 2 to 6 weeks after the myomectomy. Adhesions were scored using a 0- to 11-point scoring system. At laparoscopy, 15 of 27 incisions covered with PTFE (55.6%) and only 2 of 27 uncovered sites (7.4%) were completely free of adhesions. The mean adhesion score at the PTFE sites was significantly lower (1.88 +/- 0.46; SEM) than at the control sites (7.55 +/- 0.57). The PTFE barrier is effective in reducing postmyomectomy adhesion formation.
To assess uterine receptivity in women with unexplained infertility using integrin cell adhesion molecules as markers. Prospective, controlled study design. Eighty-seven nulliparous women with unexplained infertility and 32 fertile and infertile parous controls. Immunohistochemical staining for alpha 1, alpha 4, and beta 3 integrin subunits in endometrial biopsies obtained during the window of implantation (days 20 to 24), using the semiquantitative HSCORE by two observers in a blinded fashion. All endometrial biopsies from parous controls contained positive immunostaining for the alpha 1, and beta 3 integrin subunits in glandular epithelium. Some samples from parous controls were missing the alpha 4 subunit. In contrast, compared with parous controls, biopsies from women with unexplained infertility had reduced significantly beta 3 expression, with similar expression of alpha 1 and alpha 4. Two distinct defects in integrin "out-of-phase" samples that lacked beta 3 because of histologic lag (type I defects) and "in-phase" endometrium that still failed to express this integrin (type II defects). These subclassifications accounted for 26% and 39% of the total unexplained infertility group, respectively. Abnormal endometrial integrin expression was a frequent finding in women with unexplained infertility. These data suggest that defective uterine receptivity may be an unrecognized cause of infertility in this population of women.
Menstrual CycleExercise and Athletic PerformanceFollicular vs Luteal PhasePhysical Performance
The purpose of this study was to examine the effects of menstrual cycle phase on four selected indices aerobic capacity, anaerobic capacity, isokinetic strength, and high intensity endurance. Sixteen eumenorrheic women (VO2max > or = 50 ml.kg-1.min-1) were tested during the early follicular (F) and midluteal (L) phases of the menstrual cycle. Cycle phases were confirmed by serum estradiol and progesterone assays. No significant differences were observed between F and L tests in weight, percent body fat, sum of skinfolds, hemoglobin concentration, hematocrit, maximum heart rate, maximum minute ventilation, maximum respiratory exchange ratio, anaerobic performance, endurance time to fatigue (at 90% of VO2max), or isokinetic strength of knee flexion and extension. Both absolute and relative VO2max, however, were slightly lower in L than in F (F = 3.19 +/- 0.09.min-1, L = 3.13 +/- 0.08.min-1, P = 0.04; and F = 53.7 +/- 0.9 ml.kg-1.min-1, L = 52.8 +/- 0.8 ml.kg-1.min-1, P = 0.06). These results suggest that the cyclic increases in endogenous female steroid hormones of an ovulatory menstrual cycle may have a slight, deleterious influence on aerobic capacity, with potential implications for individual athletes. Nevertheless, the cycle phase did not impact significantly on the majority of the other performance tests and cardiorespiratory variables measured in this study.
The aim of this study was to investigate women who had first-episode psychosis within 1 year after parturition. The Danish Psychiatric Central Register and the Danish Medical Birth Register were linked to identify all women admitted for the first time to a psychiatric department in Arhus County with a psychotic episode. Fifty cases were found, giving a frequency of first-episode psychosis within 1 year after delivery of 1 per 1000. First-episode psychotic disease within the first month postpartum occurred in 1 case per 2000 deliveries. The age distribution corresponded to that of the background population, but the cases were primiparous more often than expected. The socioeconomic status was equal to that of a matched control group of obstetric patients. Birth complications did not occur more frequently than expected, but the probands had a higher risk of preterm delivery than the controls. The clinical picture of the index episode was that of manic-depressive psychosis in nearly half of the cases, but no cases of schizophrenia were found. Sixty percent of the patients had a picture of severe depression, and 20% suffered from manic disorder. The follow-up, 7 to 14 years later, was carried out by interviewing the general practitioners. Forty percent of the women had not preserved full working capacity due to mental disorder. Moreover, the follow-up pointed to schizophreniform symptoms at the index episode as a predictor of incapacity to work. Recurrences were very common (60%), especially of the nonpuerperal type, and half of the recurrences belonged to the manic-depressive disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
InfertilityClomiphene Cancer RiskOvarian Tumor EpidemiologyInfertility Treatment Outcomes
Case reports and the results of a recent case-control study have raised questions about the potential neoplastic effects of medications used as treatment for infertility. We examined the risk of ovarian tumors in a cohort of 3837 women evaluated for infertility between 1974 and 1985 in Seattle. Computer linkage with a population-based tumor registry was used to identify women in whom tumors were diagnosed before January 1, 1992. Data on infertility testing and treatment were abstracted from the medical records of women who had ovarian cancer and those of a randomly selected comparison group. The risk of ovarian tumors associated with exposure to ovulation-inducing medications was assessed through an age-standardized comparison with the rate of ovarian tumors in the general population, and Cox regression analysis was used to compare the risk of cancer among women who received these medications with the risk among infertile women who did not receive them. There were 11 invasive or borderline malignant ovarian tumors, as compared with an expected number of 4.4 (standardized incidence ratio, 2.5; 95 percent confidence interval, 1.3 to 4.5). Nine of the women in whom ovarian tumors developed had taken clomiphene; the adjusted relative risk among these women, as compared with that among infertile women who had not taken this drug, was 2.3 (95 percent confidence interval, 0.5 to 11.4). Five of the nine women had taken the drug during 12 or more monthly cycles. This period of treatment was associated with an increased risk of ovarian tumors among both women with ovarian abnormalities and those without apparent abnormalities (relative risk, 11.1; 95 percent confidence interval, 1.5 to 82.3), whereas treatment with the drug for less than one year was not associated with an increased risk. Prolonged use of clomiphene may increase the risk of a borderline or invasive ovarian tumor.
To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women.
A 3-year, multicenter, randomized, double-blind, placebo-controlled trial. A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy. Participants were randomly assigned in equal numbers (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. Four endpoints were chosen to represent four biological systems related to the (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen. Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment. Mean changes in HDL-C segregated treatment regimens into three (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status. Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia.
PCOSOvulation Induction StrategiesEndometrial Cancer RiskAntiestrogen Resistant PCOS
Women with hyperandrogenic disorders represent a unique group among those with infertility due to anovulation. Although antiestrogens are effective in restoring ovulation in most women, it remains unclear whether these treatments restore fecundability per ovulatory cycle and the ability to maintain pregnancy in these individuals. Moreover, antiestrogens are ineffective in restoring ovulation in some hyperandrogenic anovulatory women, whose condition poses unique and vexing challenges for the infertility therapist. Gonadotropin treatment in antiestrogen-resistant women often leads to ovarian hyperstimulation syndrome, which has been addressed by modification of dosing schedules (e.g., low-dose administration), pretreatment with gonadotropin-releasing hormone (GnRH) analogs, and elimination of luteinizing hormone from the administered gonadotropins. Surgical reduction in ovarian volume has met with some success, although there may be a risk of inducing surgical adhesions of the adnexa. The second major reproductive adversity facing these patients is their elevated risk of endometrial cancer. Unopposed estrogen exposure probably contributes to this risk, but hyperandrogenicity and hyperinsulinism may act independently or in concert with estrogen to amplify the risk in these women. While the risks and strategies for preventive care in these women need to be better defined, reproductive health specialists are urged to continue using presently accepted measures, including education, to maintain these women's reproductive health.
We compared energy and macronutrient intakes across the menstrual cycle in participants (n = 42) in a study that assessed the frequency of ovulatory disturbances in regularly cycling vegetarians and nonvegetarians. Women kept daily basal body temperature records for six consecutive menstrual cycles and provided 3-d diet records near the beginning, middle, and end of different cycles. On completion of the study, temperature records were quantitatively analyzed to determine whether cycles were ovulatory, and if so, the date the luteal phase began. Diet records kept near the beginning and end of cycles were matched with temperature analysis results, and women were grouped according to whether the end-of-cycle record was kept during the luteal phase of an ovulatory cycle (group 1, n = 29), or during an anovulatory cycle or before luteal phase onset of a short luteal phase cycle (group 2, n = 13). Group 1 had higher energy intakes during the luteal than during the follicular phase (9.27 +/- 2.69 vs 8.01 +/- 2.36 MJ/d, P < 0.0001), whereas intakes of group 2 did not differ across the cycle (7.91 +/- 2.18 vs 8.20 +/- 1.48 MJ/d, NS). Both groups' macronutrient intakes were similar in records kept near the beginning and end of cycles. Documentation of ovulation is necessary in studies assessing premenopausal women's energy intakes.
The present study extends a previous report of lower plasma ACTH levels in women with premenstrual syndrome (PMS) compared with asymptomatic controls. Plasma levels of estradiol and progesterone were measured daily in 10 women with confirmed PMS and 8 asymptomatic women. Daily symptom reports were maintained during the same menstrual cycle. Both estradiol and progesterone levels were consistently, but not significantly, higher throughout the cycle in PMS subjects compared with controls. From the follicular to the early luteal phase, estradiol levels were significantly higher in a previously defined PMS subgroup 2 with more severe symptoms throughout the cycle compared with both the less severe PMS subgroup 1 and controls. Progesterone levels were significantly and positively correlated with PMS symptoms along the entire menstrual cycle, preceding the symptoms by 5-7 days. These preliminary results provide support for the hypothesis that the presence of progesterone at early luteal phase levels is required for PMS symptoms to occur.
To determine whether luteal phase defect (LPD) may be an etiologic factor in ectopic pregnancy (EP). All patients who were seen over a 6-year period with the chief complaint of infertility underwent an extensive infertility workup and were followed prospectively. The diagnoses of the causes of infertility were assigned retrospectively. Two hospital-based tertiary care reproductive endocrine-infertility units. A total of 1,077 infertility patients were evaluated. Of the 633 who became pregnant, the infertility had been due to LPD in 51 and to anovulation in 210. All the infertility patients who became pregnant were followed to determine whether they miscarried, developed an EP, or had a viable birth. The incidence of EP and miscarriage in the patients whose infertility was found to be due to LPD were compared with a control group in whom the infertility was due to anovulation. The EP rate in the patients with LPD was significantly higher than in a control group whose infertility was due to anovulation (6 of 51 pregnancies versus 6 of 210 pregnancies, respectively). The spontaneous abortion rate in LPD cases also was highly significantly greater than in the control group (19 of 51 pregnancies versus 12 of 210 pregnancies, respectively). The EP and spontaneous abortion rates also were higher in patients with LPD who were untreated than in those who were treated. This study suggests that there is a significantly increased incidence of tubal EP in patients with LPD and that when patients with LPD become pregnant early ultrasound should be performed to rule out EP. The study also indicated that spontaneous abortion occurs in a significantly high percentage of LPD cases.
General OB/GYNGynecologic EndocrinologyComprehensive Review
To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations. MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes. One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure. The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94). There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.
This three-part study examined the reliability and validity of the civilian version of the Mississippi Scale for Combat-Related PTSD using data from the nonveteran participants in the National Vietnam Veterans Readjustment Study. The Civilian Mississippi Scale had a raw score distribution that was roughly symmetric, with an acceptable degree of dispersion and a reasonably high internal consistency reliability coefficient. Overall, however, measurement precision was weaker than that for the military version of the instrument, and confirmatory factor analytic findings differed from those found for the military version. Preliminary investigations of validity were in the form of correlations with indices of stressful life events, a PTSD symptom count, and measures of demoralization and active expression of hostility. The Civilian Mississippi Scale emerged from the various analyses as a PTSD measure with potential but requiring further validational study and perhaps some refinement.
Sixth grade girls (N = 224) were queried about their preparation for and expectations about menarche, their parents' roles in preparation, and their understanding of the biological basis of menstruation, characteristics of the menstrual cycle, menstrual hygiene, and menstrual-related physical and psychological changes. Although girls viewed themselves as prepared for menarche, and claimed they had discussed it with their mothers, their explanations of menstruation reflected at best incomplete knowledge, and more typically a variety of misconceptions or ignorance. In attempting to explain menstruation, they tended to focus on one particular element of the process (e.g., eggs or blood or the uterus), and were not able to integrate the elements into a comprehensive whole. Girls' knowledge of the location and function of reproductive structures was faulty, and most did not understand how they were interrelated. Girls associated a variety of negative physical and psychological changes with menstruation, indicating that although they had not yet learned the biology of menstruation, they already had learned and internalized the cultural stereotypes and myths about menstrual symptomatology. In view of reports of high levels of sexual activity, often at very young ages, and without protection, and the high risk for acquiring sexually transmitted diseases, the failure to adequately educate girls about their own anatomy and physiology has serious implications.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1994. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
This chapter has presented a somewhat complex view of the gonadotrope population, indicating that it consists of independent subsets. There may be regulatory cells that influence development and other ancillary processes needed for normal reproduction. For example, normal differentiation of PRL cells requires a functioning population of gonadotropes (Kendall et al., 1991). In addition, gonadotropes appear to be autoregulatory; subsets may produce inhibin or activin (in rats) and follistatin. Production of GnRH itself may serve as another regulatory tool. The gonadotrope population appears to be quite dynamic and convertible in the female rat. Cytological and cytochemical changes with the stage of the cycle are obvious. Increases in the numbers of immunoreactive gonadotropes parallel increases in GnRH target cells and culminate in peak expression of LH and FSH beta subunit mRNAs. The immunoreactive gonadotropes are greatly reduced after the surge activity, as though the cells had disappeared from the population. However, gonadotropes can still be detected by their content of gonadotropin mRNAs. This finding has led to the hypothesis that the gonadotropes recycle themselves. However, do they go through a resting phase? Is there a normal cycle of cell death and turnover? These are basic questions that must be answered in order to understand how the population is organized and renewed. Finally, we have returned to one of our original problems. Whereas it is clear that nonparallel release can be brought about by granules or cells with only one gonadotropin, the exact mechanisms that sort the gonadotropin molecules or turn off bihormonal expression are not known. A combination of autoregulatory events involving follistatin, activin, inhibin, and possibly steroids may play a role in modulating expression by a given subset. Delays in maturation may also prevent secretion of FSH and, hence, effect the delayed rise seen during late proestrus. The nonsecretory FSH cells seen in the studies by Lloyd and Childs (1988a) may be delayed maturers, requiring additional receptor types or changes in the calcium flux pattern to secrete their product. We also have a new question to address. What is the significance of the presence of GH in proestrous gonadotropes? Is GH a regulatory hormone, bound to receptors inside gonadotropes, or do subsets of somatotropes augment the population, producing a cocktail of GH and gonadotropins to aid ovulation? Either hypothesis is intriguing. Co-storage of GH and gonadotropins would be an efficient way of providing the hormones needed by the ovary. However, further work with in situ hybridization is needed to detect GH mRNA in such cells.(ABSTRACT TRUNCATED AT 400 WORDS)
The vascular responses to 17 beta-oestradiol were examined in 23 postmenopausal women (59 +/- 7 years [mean +/- SD]) using a placebo-controlled double-blind crossover design. All women received 1 mg 17 beta-oestradiol or placebo (P) sublingually on consecutive days in random order. Axial diameters and blood flow rates of the left common femoral arteries were determined before and 60-80 min after application of verum or placebo as well as 10-30 min after 10 mg isosorbide dinitrate (ISDN) with a quantitative duplex ultrasound technique. Oestradiol induced a vasodilation of femoral arteries (+6.4 +/- 4.1% of basal, P < 0.001 vs. basal and P), the vessel diameter was unchanged with placebo (+0.7 +/- 2.1%). The blood flow rate increased significantly after oestradiol application (+30 +/- 28%, P < 0.05 vs. basal and P), but not after placebo (+11 +/- 21%). Mean blood pressure and heart rate remained constant with both drugs. Despite its vasodilatory effect, ISDN significantly reduced the arterial blood flow after pretreatment with oestradiol and placebo, probably through cardiac preload reduction. In conclusion, 17 beta-oestradiol alters the vascular tone of systemic arteries resulting in a vasodilation and increase of blood flow. We suggest that these direct vascular actions may contribute to the preventive properties of oestrogens on cardiovascular diseases in postmenopausal women.
Ovulatory function was prospectively assessed over 6 mo in 23 vegetarians and 22 nonvegetarians with clinically normal menstrual cycles. Subjects were 20-40 y of age, of stable weight (body mass index, in kg/m2, of 18-25), on current diets for > or = 2 y, and not using oral contraceptives. Quantitative analysis of basal body temperature records classified cycles as normally ovulatory, short luteal phase (< 10 d), or anovulatory. Subjects completed the Three-Factor Eating Questionnaire (subjects completed the Three-Factor Eating Questionnaire (subscales for restraint, hunger, and disinhibition) and kept three 3-d food records. Vegetarians had lower BMIs (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < 0.05), percentage body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < 0.05), and restraint scores (6.4 +/- 4.4 vs 9.5 +/- 3.7, P < 0.05). Mean cycle lengths were similar, but vegetarians had longer luteal phase lengths (11.2 +/- 2.6 vs 9.1 +/- 3.8 d, P < 0.05). Cycle types also differed (chi 2 = 9.64, P < 0.01): vegetarians had fewer anovulatory cycles (4.6% vs 15.1% of cycles). Compared with those with restraint scores below the median, highly restrained women had fewer ovulatory cycles (3.6 +/- 2.3 vs 5.0 +/- 1.4, P < 0.05) and shorter mean luteal phase lengths (7.4 +/- 4.1 vs 10.7 +/- 3.1 d, P < 0.05). We conclude that ovulatory disturbances and restrained eating are less common among vegetarians, and that restraint influences ovulatory function.
We attempted to determine whether continuous and cyclic medroxyprogesterone acetate modulates the effects of estrogen on dilation of atherosclerotic coronary arteries in surgically postmenopausal female monkeys. Estrogen replacement in postmenopausal women preserves normal dilator responses of atherosclerotic coronary arteries. The effects of progestins on coronary artery reactivity have not been determined. Repeated quantitative coronary angiography was used to study the effects after 1 month of 1) no hormone replacement (control) or oral administration of 2) continuous conjugated equine estrogens, 3) cyclic high dose medroxyprogesterone acetate (MPA) given on days 16 to 26 of the month, 4) conjugated equine estrogens plus continuous low dose MPA, or 5) conjugated equine estrogens plus cyclic high dose MPA on endothelium-mediated dilation of atherosclerotic coronary arteries in 12 cynomolgus monkeys. Change in diameter of the left circumflex coronary artery was measured in response to intracoronary infusions of acetylcholine (10(-6) mol/liter per min) and nitroglycerin (15 micrograms/min). Coronary arteries constricted during no hormone treatment (-8 +/- 3% [mean +/- SEM]), dilated during conjugated equine estrogen treatment (+3 +/- 1%, p < 0.05 vs. control) and constricted during cyclic MPA treatment (-3 +/- 2%). Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen inhibited acetylcholine responses by 50% (p < 0.05 vs. conjugated equine estrogens). There was no effect of treatment on vascular response to nitroglycerin (p > 0.05). Treatment with conjugated equine estrogens, but not MPA, augmented endothelium-mediated dilation of atherosclerotic coronary arteries. Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen diminished endothelium-mediated dilation.
To document the abnormal findings at hysteroscopy and laparoscopy in patients with chromic pelvic pain. Prospective evaluation at surgery of women treated consecutively between January 1, 1991, and December 30, 1992. A private practice. One hundred forty-one women with pelvic pain (average age 35 yrs). Laparoscopy was performed in all patients, and hysteroscopy in all but one, who had had a hysterectomy. Endometrial and endocervical biopsies were performed. MAIN In 42 (30%) of 140 patients with a primary diagnosis of chronic pelvic pain hysteroscopic evaluation with endometrial and endocervical biopsies revealed an abnormality. Findings at hysteroscopy included leiomyomas in 25 patients (18%), intrauterine polyps in 9 (6.4%), and cervical stenosis in 4 (2.9%). Three women (2.1%) had intrauterine scarring and one (0.7%) had a bicornuate uterus. Endometrial biopsies showed adenomatous hyperplasia with atypia, and cystic hyperplasia in one patient each. Endocervical biopsies revealed cervical dysplasia in four women (2. 89%). An abnormal finding was documented on laparoscopic examination in all 141 patients. These included endometriosis in 113 patients (80%), adhesions in 67 (48%), leiomyomas in 59 (42%), and enlarged globular uterus in 34 (24%). In addition, appendiceal abnormalities were present in three women (2.1%) and hernia in two (1.4%). Hysteroscopic abnormalities were found in 30% and laparoscopic abnormalities in 100% of patients who had a primary diagnosis of chronic pelvic pain.
To investigate the efficacy of hCG in the management of recurrent early pregnancy loss. A prospective, randomized, controlled trial. Miscarriage Clinic, Women's Hospital, Liverpool, United Kingdom. Eighty-one women attending the miscarriage clinic with idiopathic recurrent pregnancy loss were randomized to receive hCG supplementation or placebo in early pregnancy. The success rate or live birth rate. In women with regular menstrual cycles it was found that hCG had no beneficial effect, the pregnancy success rate being 86% in both groups. However, women with oligomenorrhea had a pregnancy success rate of 40% in the placebo group but a statistically significant improvement to 86% if hCG was given. Human chorionic gonadotropin can be recommended for idiopathic recurrent pregnancy loss in women with oligomenorrhea.
The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.
Fertility AwarenessInterest and AttitudesAdoption and BarriersPatient Preferences
Although modern methods of natural family planning (NFP) are effective both to avoid and to achieve pregnancy, relatively few women use these methods. It is not known whether this is due primarily to lack of interest or to other factors. We therefore explored the level of interest in NFP among female family practice patients. We mailed information about NFP to 400 female patients between ages 21 and 42 and conducted follow-up interviews by telephone. We excluded 162 women for whom we could not obtain accurate addresses or phone numbers, 68 women we could not reach by telephone, 67 women who were not currently at risk of pregnancy, and 15 women for other reasons. Twenty-eight women refused to participate in the study. Sixty women completed telephone interviews. Forty-three percent of respondents (n = 60) were interested in learning more about NFP, 24% said they were likely to use NFP to avoid pregnancy, and 32% were likely to use NFP to achieve pregnancy. Younger women and women who were Christian but not Catholic and not of a major Protestant denomination were more interested in NFP. Some female family practice patients are interested in learning and using NFP.
To determine pharmacokinetic and endometrial effects of vaginally delivered micronized P. Functionally agonadal estrogen-replacement recipients received either micronized P administered vaginally or bi-daily IM injections of P. Hourly blood samples were obtained, from baseline to 6 hours after the initial dose of P and again on simulated cycle day 21 when transvaginal ultrasound (US) measurements and tissue samples of the endometrium were performed. Blood and tissue samples were assayed for P. Endometrial histology, estrogen receptor (ER) and P receptor (PR) contents were evaluated. University of Southern California School of Medicine, Los Angeles, California. Twenty functionally agonadal and four normally ovulating women. Delivery differences were assessed by [1] endometrial P concentrations; [2] USs; [3] histologic datings; [4] ER and PR contents, and [5] serum P levels. Endometrial P concentrations were higher with vaginally administered P than endometrial concentrations observed in normal ovulatory women or women who consistently had the highest serum P after IM administration (11.50 +/- 2.60 versus 1.40 +/- 0.40 versus 0.30 +/- 0.10 ng/mg protein [36.56 +/- 8.27 versus 4.45 +/- 1.27 versus 0.95 +/- 0.32 nmol/L], respectively). After 7 days of P, no differences between either treatment regimen and control groups were detected by histologic, ultrasonographic, or immunocytochemical receptor analyses. Vaginal micronized P enhances P delivery to the uterus compared with a standard IM regimen and results in a synchronous secretory endometrial histology in agonadal women preparing for embryo donation.
To assess the efficacy of alprazolam in the treatment of two groups of patients diagnosed with late luteal phase dysphoric disorder (LLPDD). The first group met only the diagnostic criteria for LLPDD. The second group experienced LLPDD and mild symptoms of anxiety and depression during the follicular phase. A double-blind, placebo-controlled crossover design was used. Patients were treated with alprazolam and placebo for 3 months each and completed daily measures of anxiety, tension, depression, irritability, and feelings of being out of control. The response to alprazolam differed significantly by group. For the first group, alprazolam (0.25 mg three times a day) relieved the severity of tension (P = .001), irritability (P = .005), anxiety (P = .008), and feelings of being out of control (P = .012) more than placebo. Few side effects were reported; the incidence (P = .001) and severity (P = .001) of side effects were dose-related. Alprazolam and placebo did not differ for the second group, and the incidence and severity of side effects were unrelated to dose. Alprazolam benefits women diagnosed solely with LLPDD. It is not recommended for patients who experience LLPDD as well as symptoms of mild anxiety or depression during the follicular phase.
PCOSBreast Cancer RiskBreast Cancer AssociationHyperandrogenism and Anovulation
Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.
To determine whether long-term intravenous (IV) tocolysis using combined terbutaline and magnesium sulfate is safe and effective. One thousand consecutive women in preterm labor were treated with combination IV tocolytic therapy. Terbutaline was initiated with an infusion rate of 1.75 micrograms/minute and increased to a maximum of 80 micrograms/minute. Magnesium sulfate was infused at 2 g/hour without any bolus and increased to maintain a serum level of 6.5-7.5 mg/dL. Tocolysis was continued until fetal lung maturity was achieved or delivery occurred. Combination tocolytic therapy prolonged pregnancy by a mean (+/- standard deviation) of 61 +/- 23.6 days in 751 women with intact membranes and by 20.5 +/- 17.4 days in 249 with ruptured membranes. The longest durations of continuous IV tocolysis were 123 days in a patient with intact membranes and 77 days in one with ruptured membranes. The most common side effects were nausea and vomiting, followed by chest tightness and shortness of breath. Long-term IV tocolysis appeared to be safe and to have acceptable side effects, allowing patients to receive combined terbutaline and magnesium sulfate until delivery.
Fertility AwarenessPsychosocial OutcomesRelationship QualitySpiritual and Psychological Impact
To clarify how often infertile men should have intercourse to achieve conception, the effect of sequential ejaculation on total motile sperm counts was investigated.
Case-control study.
Infertility and IVF unit, tertiary care center. Five hundred seventy-six men who produced two closely spaced sequential ejaculates.
The total motile sperm counts of the second ejaculates were compared with the total motile sperm counts of the first ejaculates. In normospermic men (n = 359), the total motile sperm counts decreased significantly from 93 (18 to 601) (median [minimum to maximum] x 10(6)) in the first ejaculate to 42 (1.2 to 387) in the second ejaculate, produced 24 hours later. In contrast to the normospermic men, in the asthenospermic group (24 hours difference, n = 81) and in both oligospermic groups, (1 to 4 hours difference, n = 27; and 24 hours difference, n = 45), there were no significant changes in the total motile sperm counts (24 [5.9 to 229] versus 30 [0.8 to 150], 6 [0.8 to 18] versus 3.6 [0.1 to 63] and 13 [2.5 to 32] versus 10 [0.1 to 66], respectively). Moreover, in both oligoasthenospermic groups (1 to 4 hours difference, n = 23; and 24 hours difference, n = 41) the total motile sperm counts increased significantly (3.2 [0.6 to 7.9] versus 8 [0.4 to 48] and 4 [0.2 to 13] versus 4 [0.1 to 101], respectively). In all groups, pooling sequential ejaculates significantly increased the total motile sperm counts, over and above that of the first ejaculate, by 49% in the normospermic group, 95% in the asthenospermic group, 67% and 75% in the oligospermic groups (1 to 4 hours and 24 hours difference, respectively), and 233% and 139% in the oligoasthenospermic groups (1 to 4 hours and 24 hours difference, respectively). Sequential ejaculation may overcome the impaired sperm transport causing low total motile sperm counts observed in some oligospermic and/or asthenospermic men. Most of these infertile men may significantly increase their fertility potential, assessed by the total motile sperm counts, either by pooling sequential ejaculates for IUI, GIFT, and IVF, or by having intercourse every day or even twice a day, at the time of ovulation.
To determine the ability of luteal phase length determined by basal body temperature (BBT) pattern and a midluteal serum progesterone level to predict the result of an endometrial biopsy in a subsequent cycle. We performed a retrospective analysis of 141 women with a history of infertility who were being evaluated for luteal function. The luteal phase length determined from a BBT chart of one menstrual cycle was compared to a single midluteal serum progesterone level from a second menstrual cycle. These findings were compared to a luteal phase endometrial biopsy performed in a third menstrual cycle. Subjects were divided into four groups depending upon luteal phase length (normal 11 or more days) and serum progesterone level (normal at least 10 ng/mL). The four groups were designated "normal," "short luteal phase," "low progesterone," and "abnormal," depending upon the results of the two tests. The frequency of in- and out-of-phase endometrial biopsy results in the four groups was compared. There was no difference in the occurrence of an in- or out-of-phase endometrial biopsy when the four groups were compared. Neither luteal phase length nor a single midluteal serum progesterone level was predictive of subsequent in-phase or out-of-phase endometrial biopsy.
Insufficient breast milk is the most common reason for premature termination of breast-feeding. The causes of lactation insufficiency are usually multifactorial; in a small percentage of cases it is due to primary lactation failure of unknown origin. The aim of this study was to investigate whether lactation insufficiency of unknown origin could be caused by serum lactogens that had reduced biological activity.
Women with lactation insufficiency of unknown origin and normal lactating controls were subjected to a standardized breast-feeding test for assessment of milk production. Thirty minutes later, serum samples were obtained for determination of total lactogen bioactivity, using an in-vitro bioassay, and levels of prolactin (PRL) and growth hormone (GH) using radioimmunoassay (RIA). Twelve lactating mothers with a clinical diagnosis of lactation insufficiency of unknown origin were compared with 12 matched mothers with normal lactation. The Nb2 lymphoma cell bioassay was used to measure total lactogen bioactivity in sera. Conventional RIA kits were used to estimate serum PRL and GH concentrations. Mean milk yield on standardized test feed was 21.6 ml for patients and 146.5 ml for controls. In both patient and control groups the total serum lactogen bioactivity ranged from about 150 to 5000 mIU/l, while the serum RIA (PRL+GH) levels ranged from about 350 to over 7000 mIU/l. There was no evidence of lactogens with reduced bioactivity in the patients' sera. Lactation insufficiency in the women studied cannot be explained by serum lactogens that possess unusually low bioactivity.
Research on inflammatory bowel disease risk among oral contraceptive users has reached conflicting conclusions. This population-based case-control study evaluated the effects of oral contraceptive use on ulcerative colitis and Crohn's disease risk. Cases were women enrollees, aged 15-68 years, of Group Health Cooperative of Puget Sound (a prepaid health plan based in western Washington State) who had ulcerative colitis (n = 211) or Crohn's disease (n = 91). Age-matched controls were randomly selected from the health plan enrollment file. An in-person interview obtained information about lifetime contraceptive use. Conditional logistic regression analysis was used to estimate relative risks and 95% confidence intervals for disease. Women who reported oral contraceptive use within 6 months before disease onset were at increased risk for both diseases compared with never users (relative risk (RR) of ulcerative colitis = 2.0, 95% confidence interval (CI) 1.2-3.3; RR of Crohn's disease = 2.6, 95% CI 1.2-5.5). Women who had used oral contraceptives for more than 6 years had the highest risk of Crohn's disease (RR = 5.1, 95% CI 1.8-14.3). In contrast, increasing duration of use was not associated with increased risk of ulcerative colitis. Adjustment for race, smoking, income, or pregnancy history did not substantially alter these results. Higher ulcerative colitis risk tended to occur among users of high estrogen dose oral contraceptives, while Crohn's disease risk was similar regardless of estrogen potency.
InfertilityPregnancy Outcome AssociationMiscarriage Risk FactorsSubfertility Association
To examine the relationship of subfertility with miscarriage, low birth weight, and preterm delivery. Comparison of time to pregnancy distributions between pregnancies that had different outcomes. (a) miscarriages with live births; within live births, (b) low birth weight infant (up to 2,500 grams) or not low birth weight; (c) preterm birth (37 weeks or less) or not preterm. Cox regression was used to adjust for covariates. All first pregnancies were analyzed from the National Child Development Study, a large survey of young adults aged 33 years, which is nationally representative of the British-born population. The distribution of the time taken to conceive (time to pregnancy), miscarriage, birth weight, and preterm delivery. Pregnancies that ended in miscarriage tended to take 23% longer to conceive, after adjustment for the other variables. Pregnancies that resulted in preterm delivery tended to take 15% longer to conceive. There was no statistically significant association with low birth weight. Delay in time to conception is a risk factor for poor obstetric outcome, irrespective of medical intervention.
Menstrual CycleMineral DeficiencyEtiologyTrace Element Assessment
We measured plasma Cu. Zn and Mg levels in 40 women suffering from premenstrual tension syndrome (PMTS) and in 20 control subjects by atomic absorption spectrophotometer. Mean plasma Cu, Zn and Mg levels, the Zn/Cu ratio were 80.2 +/- 6.00 micrograms/dl, 112.6 +/- 8.35 micrograms/dl, 0.70 +/- 0.18 mmol/l, and 1.40 +/- 0.10 in the PMTS group; and 77.0 +/- 4.50 micrograms/dl, 117.4 +/- 9.50 micrograms/dl, 0.87 +/- 0.10 mmol/l, and 1.51 +/- 0.05 in the control group respectively. The mean Mg level and the Zn/Cu ratio were significantly lower in PMTS patients than in the control group. Plasma Mg and Zn levels were diminished significantly during the luteal phase compared to the follicular phase in PMTS group. Mg deficiency may play a role in the etiology of PMTS.
To examine whether luteal E2 is obligatory for obtaining an adequately developed endometrium. Survey of women with premature ovarian failure (POF) in a prospective, controlled, randomized study. In vitro fertilization unit in a tertiary care university medical center. Fourteen amenorrheic women with POF, candidates for oocyte donation, were divided into two distinct groups with seven women in each subgroup. Endometrial priming with a fixed dose of oral micronized E2, 4 mg/d for 14 days, was similarly performed in the study and the control groups. Progesterone replacement during the luteal phase was also identical in the two groups and was accomplished by IM P in oil, 50 mg/d for another 14 days. Only the control group continued to have the same E2 regimen during the luteal phase. Follicular phase mean E2 levels as well as luteal phase mean P levels were similar in both groups. However, luteal E2 levels differed significantly between the study and the control groups (21 +/- 5 and 692 +/- 199 pg/mL, respectively; conversion factor to SI units, 3.671). Nevertheless, histologic evaluation of endometrial biopsies on days 21 and 26 were similar for both groups. Endometrial gland dating, using light microscopy in the study and the control groups, on day 21, was 19.1 +/- 0.8 and 18.4 +/- 0.5, respectively, and on day 26, 25.4 +/- 0.8 and 25.9 +/- 0.5, respectively. Dating of the stroma in the two biopsies was also similar in both groups. Moreover, transmission electron microscopy performed in two patients of the study group showed typical characteristics of a secretory endometrium. Luteal E2 depletion in the human does not seem to adversely affect the morphological developmental capacity of the endometrium. Our results suggest that E2 secretion by the corpus luteum in the human does not appear to be obligatory for the development of a normal secretory endometrium. The actual receptivity of the endometrium after such preparation needs to be evaluated.
Reproductive EndocrinologyDiagnostic AccuracySensitivity and SpecificityLuteal Phase Defect Detection
To assess the sensitivity and specificity of common clinical tests used for the diagnosis of luteal phase defect (LPD). The sensitivity and specificity of these tests for predicting low integrated P levels over the luteal phase were calculated. Outpatient reproductive endocrinology and infertility clinic at a university medical center. Fifty-eight strictly defined normal women were used to determine normal integrated luteal phase P levels. The study population was a separate 34 women who either were normal (n = 15) or were being evaluated for infertility or recurrent abortion (n = 19). These 34 study subjects all had the following tests performed daily reproductive hormone levels, daily assessment of preovulatory follicle size, late luteal endometrial biopsies, and BBT charts. Basal body temperature, maximum preovulatory follicle size, dated endometrial biopsies, and serum P levels (single and multiple) were used in an attempt to predict which patients had low integrated P levels. Unacceptably low sensitivity and/or specificity levels were appearance of BBT charts, luteal phase length, and preovulatory follicle diameter. Timed endometrial biopsy was found to have marginally acceptable sensitivity and specificity levels whether dated by next menstrual period or midcycle events. The best test for the prediction of low integrated P was a single serum P level from the midluteal phase that was < 10 ng/mL (31.8 nmol/L) or a sum of three random serum P measurements that was < 30 ng/mL (95.4 nmol/L) (also obtained in the midluteal phase). Luteal phase defect is a relatively uncommon but important cause of infertility and/or habitual abortion. The recommended test for the determination of LPD is a midluteal phase single serum P level < 10 ng/mL or the sum of three serum P levels that is < 30 ng/mL. The endometrial biopsy is a second line test that is only recommended when LPD needs to be evaluated in a treated cycle (ovulation induction or supplemental P).
To follow-up and expand discussion on the action mechanisms of antisperm antibodies in human infertility, the etiology and control of antisperm antibody induction, sperm antigens involved in immunoinfertility, and strategies for therapy.
A review of the recent literature with an emphasis on female immunoinfertility. The role of antisperm antibodies in clinical infertility continues to be defined. Through assisted reproductive technologies, antisperm antibodies were shown to exert detrimental effects on different prefertilization and possibly postfertilization events. The female reproductive tract is part of the common mucosal immune system and is able to mount effective immune responses against infectious agents, foreign antigens, and, occasionally, sperm cells. Sperm membranes and constituents contain numerous antigenic components foreign to the human body, and yet antisperm antibodies become problematic in few women exposed to semen. Semen and sperm cells contain immunosuppressive factors capable of inhibiting different immune cells. Fertile women apparently produce antisperm antibodies but also possess neutralizing serum anti-idiotypic antibodies that are lacking in virgin and immunoinfertile women. Antisperm antibodies can affect adversely human fertility but normally may be controlled by anti-idiotypic antibodies, which along with immunosuppressor factors in semen prevent their induction to a significant degree. This balance between detrimental and "beneficial" immune response to sperm may be shifted toward an antisperm antibody response by stimulatory factors such as infection. Therapies may be devised to stimulate the anti-idiotypic antibody system, to induce immune tolerance to sperm antigens, and to use antigens to adsorb antisperm antibodies from spermatozoa.