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PubMed1989

Endometrial glandular haemosiderosis in homozygous beta-thalassaemia.

Female patients with beta-thalassaemia major usually suffer from hypogonadotropic hypogonadism associated with amenorrhea, anovulation and infertility, attributed to the deposition of haemosiderin in the pituitary gland as well as in the ovaries. Pregnancies are rare and, with few exceptions, occur mainly in patients with beta-thalassaemia intermedia. Our study presents histopathological evidence that deposition of haemosiderin occurs in the endometrial glandular epithelium of 3 patients with beta-thalassaemia major. This deposition is mainly evident in the apical part of these cells above the nuclei, and should be taken into consideration as a contributing factor to the infertility in these patients by altering endometrial receptivity for implantation. In 2 patients who received effective iron chelating treatment with desferrioxamine the endometrial haemosiderin deposits either disappeared (patient C.R.), or were significantly reduced (patient G.L.).

Adult↗
PubMed1991

Screening infertile women for the assessment of corpus luteal function and their response to therapy by ELISA of pregnanediol glucuronide.

Corpus luteal function was assessed by estimating pregnanediol 3-alpha-glucuronide (PdG) in three midluteal-phase urine samples collected from 85 women attending the infertility clinic. The previously established cut off limits based on PdG estimations were useful in detecting anovulation in 23 cases, corpus luteal adequacy in 42 cases and corpus luteum deficiency (CLD) in 20 cases. In 8 women CLD could be corrected with 50 mg of clomiphene citrate (CC) therapy whereas 6 women required 100 mg of CC and 3 pregnancies were achieved. This rapid screening method is thus useful in segregating a large number of women according to their ovulatory status and in the subsequent treatment of CLD.

Clomiphene↗
PubMed1993

Ovulation induction in polycystic ovary syndrome: a review of conservative and new treatment modalities.

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogeneous clinical and endocrine features. Chronic anovulation and infertility are common and affect about 75% of the patients. Ovulation induction in PCOS patients is a challenge for the physicians who treat these patients. Several different treatment modalities have been proposed to induce ovulation in PCOS, each of which deals with a different clinical or endocrine disorder which is present in these patients. This review presents traditional and new methods for ovulation induction in PCOS patients, the theoretical background, the pros and cons for each treatment and success rate.

Clomiphene↗
PubMed1995

The effect of consecutive cycles of clomiphene citrate therapy on endometrial thickness and echo pattern.

OBJECTIVE: To determine whether successive cycles of clomiphene citrate affect endometrial thickness. METHODS: Thirty-four women presenting for treatment of anovulation, oligoovulation, or follicle maturation defects were given the smallest dose of clomiphene citrate necessary to attain a mature follicle. If no pregnancy ensued, the same dose was continued if a follicle 18-24 mm in diameter and a serum estradiol (E2) level greater than 200 pg/mL were achieved. Ethinyl E2 was supplemented for poor cervical mucus only. Endometrial thickness and echo patterns were measured each cycle at peak follicular maturation. RESULTS: There was no difference in mean endometrial thickness during the first six cycles of therapy, nor was there a trend for thickness to increase or decrease with successive cycles with or without the addition of ethinyl E2. There was no change in the distribution of echo patterns with successive cycles of clomiphene citrate. Post-treatment measures of thickness and echo pattern did not differ from baseline pre-treatment values. The homogeneous hyperechogenic pattern was the rarest. Mean serum E2 and progesterone levels at mid-cycle did not change with successive cycles. CONCLUSION: One proposed mechanism for the dichotomy between ovulation and pregnancy rates after clomiphene citrate therapy is that the drug adversely affects the endometrium. If clomiphene citrate does affect implantation adversely, the mechanism does not seem to be related to thinning the endometrium or causing an echo pattern that indicates a poor prognosis. The data also suggest that estrogen supplementation does not influence endometrial thickness and would best be used exclusively for hostile cervical mucus.

Adult↗
PubMed1994

Follicular and FSH responses to parturition during the anovulatory season in mares.

The ovaries of periparturient pony mares (n=9 to 16 parturitions per month for January to April) were scanned ultrasonically on the day of parturition, while those of postpartum and control mares (n=12) were examined at least twice weekly. Four mares had apparent lactational anovulation (incidence, 7%) that corrected spontaneously (1 mare) or within 14 d after the weaning of foals on August 10 (3 mares). All but 2 of the postpartum ovulations occurred after April 29; that is, parturition did not effectively stimulate ovulation in ponies foaling during the anovulatory season. Mean diameter of the largest follicle per month increased (P<0.001) progressively in the controls (means: 11.4, 14.4, 19.0 and 24.5 mm for January to April, respectively). In the parturient mares, the diameter of the largest follicle on day of parturition did not increase over months (range of means: 13.6 to 16.9 mm), indicating that a suppressive effect of pregnancy counteracted the stimulatory effect of season. Within each month of parturition, diameter of the largest follicle increased (P<0.05) between Day 0 (day of parturition) and Day 3 or 7. Blood samples for FSH assay were taken daily for 14 d from 6 mares with parturition in the middle of each month and from 6 controls on the corresponding calendar days. In periparturient mares, a significant increase in mean FSH concentrations occurred for all months of parturition between Day-2 and Day 0, followed by a significant decrease between Day 3 and Day 7. Maximum means for the periparturient FSH profile were temporally related to the beginning of follicular growth. In the controls, FSH concentrations were not affected by month or day, or by their interaction. Within each month, mean FSH concentrations were lower (P<0.05) in the periparturient mares than in the controls (averaged over all months: 3.9+/-0.1 versus 7.9+/-0.3 ng/ml) even though follicular growth was greater following parturition than during the corresponding calendar days in controls.

Journal Article↗
PubMed1995

Ultrasonography and endocrinology of ovarian dysfunctions induced in heifers with estradiol valerate.

This study monitored the long-term follicular dynamics and changes in ovarian steroid hormones associated with an experimental model of cystic ovarian degeneration (COD) in the heifer. In the treated group (n = 7), Holstein heifers received a single injection of 500 microg of cloprostenol (prostaglandin F2a, PG) and 5 mg of estradiol valerate (EV) on either Day 17, 18 or 19 of the estrous cycle. The control group (n = 7) received only PG. Transrectal ultrasound was performed daily, beginning 8 to 10 d before injection and continuing until a return to normal cyclicity (40 to 74 d). Blood samples were taken twice daily over the same period. The EV disrupted the normal follicular development as well as the plasma progesterone and estradiol profiles of 6/7 heifers in the treated group. Two different types of responses were observed. The Type-I response (n = 2) was characterized by a premature ovulation followed by a corpus luteum (CL) which persisted for over 30 d. The Type-II response (n = 4) was characterized by anovulation followed by the emergence of a large ovarian structure which could further be subtyped. In Type- IIA (n = 2), this follicle ovulated at an exaggerated size of 19 or 24 mm (mean diameter of controls: 13.4 +/- 2.7 mm). The subsequent cavernous CL was very large at 35 and 37 mm (mean diameter of CL in controls: 23.8 +/- 2.0 mm). In Type- IIB (n = 1), the follicle present at the time of injection continued to grow and became a luteinized cyst. In Type-IIC (n = 1), several waves of follicular cysts developed and persisted for 52 d. This study suggests that EV induces a range of ovarian dysfunctions including different forms of COD. The individual differences in the stage of folliculogenesis at the time of injection of EV may be responsible for the different types of responses.

Journal Article↗
PubMed1991

Contraceptive effects of extended lactational amenorrhoea: beyond the Bellagio Consensus.

We have recorded the duration of lactational anovulation and amenorrhoea in a well-nourished group of Australian women who breastfed their babies throughout the study. The data enabled us to compare the theoretical cumulative probability of conception among breastfeeding women who had unprotected intercourse irrespective of their menstrual status with that of those who had unprotected intercourse only during lactational amenorrhoea. Breastfeeding alone is not an effective form of contraception, since all the women in our study resumed normal ovulation while still breastfeeding. However, among women who have unprotected intercourse only during lactational amenorrhoea but adopt other contraceptive measures when they resume menstruation, only 1.7% would have become pregnant during the first 6 months of amenorrhoea, only 7% after 12 months, and only 13% after 24 months. Thus for our women it would be possible to extend the Bellagio Consensus Conference guidelines which stated that lactational amenorrhoea can only be relied on as a contraceptive for the first 6 months post-partum in women who are fully or almost fully breastfeeding. The lactational amenorrhoea method can be relied on for excellent contraceptive protection in the first 6 months of breastfeeding, irrespective of when supplements are introduced into the baby's diet; for women who continue to breastfeed the method can also give good protection for up to 12 months post partum. Once menstruation has returned, other forms of contraception are essential to prevent pregnancy.

Amenorrhea↗
PubMed1982

Infertility and the physician--patient relationship: a biopsychosocial challenge.

Research to date has not been able to dispel controversy over the question of "psychogenicity" of infertility. Increasing numbers of studies suggest that neuroendocrinological factors play a role in what is most likely a multidetermined condition. Whatever the etiology, and whether infertility occurs spontaneously (e.g., anovulation) or by choice (e.g., surgical sterilization), the physician must be alert to the special needs of the patient, to the environmental setting, and to the intricate interplay between infertility and emotional reaction. The physician-patient relationship as a triadic rather than dyadic relationship introduces unique transference and counter-transference considerations which must be an acknowledged part of evaluation and treatment.

Adaptation, Psychological↗
PubMed1992

Active immunization of baboons (Papio anubis) with the bovine LH receptor.

Four baboons (Papio anubis) were actively immunized with bovine LH receptor for periods of 6-22 months. Serum antibody levels were measured by an enzyme immunoabsorbant assay (ELISA). Antibodies against the receptor were detected 2 weeks after the first injection. Antisera caused an inhibition in the binding of human chorionic gonadotropin (hCG) to its receptor as well as inhibited the production of hCG induced testosterone by rat Leydig cells in culture. Serum estradiol and progesterone levels were determined by radioimmunoassay (RIA). Progesterone levels were suppressed during the post immunization period. Two baboons experienced periods of anovulation. Serum estradiol levels were cyclic and appeared elevated. Baboons were mated with males of proven fertility; none of the immunized females conceived over eight cycles of observation. Fertility parameters returned to normal, when antibodies against LH-receptor were undetectable in the serum.

Animals↗
PubMed1983

Maternal and child nutritional status: its association with the risk of pregnancy.

Breastfeeding reduces the interval between births by its effect on prolonging the period of postpartum anovulation and in some cases, reducing the likelihood of conception once ovulation has occurred. Extended durations of postpartum amenorrhea (18 months and longer) are observed among many women in developing countries, while shorter durations (6 months or less) are common among women in developed countries. This differential effect has been suggested to be related to maternal nutritional status, but numerous other factors also differ. This paper reviews the literature in this area, and suggests that most studies indicate a small and demographically insignificant effect of maternal nutritional status on the period of postpartum amenorrhea. Factors associated with suckling patterns appear to be more important in determining the length of postpartum infertility. Suckling frequency and intensity which affects the hormonal stimulus preventing ovulation appear to be affected by the type of and how supplemental feeding is given to the child (use of bottles), whether suckling is on demand or scheduled, the frequency of night-time feedings (influenced by whether or not the mother sleeps with the child), whether or not pacifiers are used, and the child's nutritional and health status.

Amenorrhea↗
PubMed1996

Evaluation of the postcoital test for assessment of 'cervical factor' infertility.

OBJECTIVE: To evaluate the test properties of the postcoital test (PCT). STUDY DESIGN: Retrospective analysis of prospectively collected data on a cohort of infertile couples with complete follow up. SETTING: Fertility clinic of a Dutch university hospital. SUBJECTS: A continuous series of 224 couples of whom 24 were excluded for reasons of anovulation, coital problems, proven sterility or incomplete follow-up. ANALYSIS: Cumulative pregnancy rates in relation to PCT results with and without treatment for 'cervical factor' infertility. RESULTS: The predictive values of normal and abnormal PCTs were 0.54 and 0.58 overall and 0.74 and 0.47 if only untreated women were considered. Sensitivity and specificity were, respectively, 0.47 and 0.65 for all women and 0.54 and 0.68 for untreated women only. Likelihood ratios for normal and abnormal PCTs were 0.83 and 1.32 overall and 0.67 and 1.72 in untreated women. CONCLUSION: The PCT has poor predictive power. This and the psychological impact on subfertile couples attest to the need for more rigorous study designs in evaluating this test.

Adult↗
PubMed1989

The etiology of polycystic ovary syndrome (PCO).

Consideration of existing data leads to the hypothesis that polycystic ovary syndrome results from a primary abnormality in the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis characterized by increased IGF-1 activity at multiple sites. The effect of elevated IGF-1 activity upon the ovary, the adrenal, and on peripheral tissues may lead to the clinical and biochemical features of PCO, including hyperandrogenemic chronic anovulation, insulin resistance, and elevated adrenal androgen secretion. The fundamental defect may be a consequence of feeding behavior early in life.

Female↗
PubMed1995

A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density.

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2-3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E1) and 17-beta-estradiol (E2) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E2. During the next 3 years, the levels of E2 and E1 showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), delta 4-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E1, E2 and T. BMI correlated positively with E1 and E2. The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.

Androstenedione↗
PubMedDate not supplied

Changes of ovarian hormonal function with aging.

Striking changes of ovarian function occur with aging. These changes begin subtly with reductions of fecundability being observed after age 25. The transition from reproductive to postreproductive life is characterized by menstrual irregularity including anovulation, or short luteal phases. The most prominent hormonal changes at the menopause are drastic reductions of estradiol and progesterone secretion by the ovary, reflecting the cessation of folliculogenesis and ovulation. Elevations of gonadotropins and reduction of inhibin levels also reflect the loss of folliculogenesis and ovulation. There are accompanying decreases of ovarian androgen secretion; however, the postmenopausal gonad directly secretes more testosterone after, than before, the menopause.

Aging↗
PubMed1991

Toxic effects of cadmium on LHRH-induced LH release and ovulation in rats.

CFY rats were given 5 or 10 mg/kg bw cadmium chloride (CdCl2) or 0.9% NaCl solution (1 mL/kg) subcutaneously on the day of diestrus II. Six days later (proestrus) at 1200 h they were anesthetized with pentobarbital, 0.5 or 2 micrograms/kg LHRH was injected intravenously at 1400 h, and blood was collected for LH determination. A second group of animals pretreated with 10 mg/kg bw CdCl2 and treated with 2 or 4 micrograms/kg LHRH was allowed to recover from the anesthesia and checked for ovulation the next day (estrus). In rats treated with 10 mg/kg of CdCl2, the LH content of pituitary gland diminished, but no significant difference was found in the LH response to LHRH. In controls (ovulation blocked by anesthesia) 2 as well as 4 micrograms/kg of LHRH completely restored ovulation, while after Cd pretreatment, ovulation recovered depending on the dose of LHRH. It is concluded that Cd-induced anovulation is related to altered function of the pituitary gland and ovary, which can be restored by excess LHRH.

Animals↗
PubMed1995

Circulating and ovarian IGF binding proteins: potential roles in normo-ovulatory cycles and in polycystic ovarian syndrome.

IGFs function as co-gonadotropins in the ovary, facilitating steroidogenesis and follicle growth. IGFBP-1 to -5 are expressed in human ovary and mostly inhibit IGF action in in vitro ovarian cell culture systems. In the clinical disorder of polycystic ovarian syndrome (PCOS), which is characterized by hyperandrogenemia, polycystic ovaries and anovulation, follicles have a higher androgen: estradiol (A : E2) content and growth is arrested at the small antral stage. In the PCOS follicle, follicle stimulating hormone (FSH) and IGF levels are in the physiologic range, and even in the face of abundant androstenedione (AD) substrate, aromatase activity and E2 production are low. When PCOS granulosa are removed from their ovarian environment, they respond normally or hyperrespond to FSH. It has been postulated that an inhibitor of IGF's synergistic actions with FSH on aromatase activity may be one (or more) of the IGFBPs, which contributes to the arrested state of follicular development commonly observed in this disorder. High levels of IGFBP-2 and IGFBP-4 are present in follicular fluid (FF) from androgen-dominant follicles (FFa) from normally cycling women and in women with PCOS. This is in marked contrast to the near absence of these IGFBPs in estrogen-dominant FF (FFe), determined by Western ligand blotting. Regulation of granulosa-derived IGFBPs is effected by gonadotropins and insulin-like peptides. In addition, an IGFBP-4 metallo-serine protease is present in FFe, but not in FFa in ovaries from normally cycling women and those with PCOS, although the IGFBP-4 protease is present in PCOS follicles hyperstimulated for in vitro fertilization. Recent studies demonstrate that IGF-II in FFe is higher than in FFa' whereas IGF-I, IGFBP-3 and IGFBP-1 levels do not differ, underscoring the importance of local IGF-II production by the granulosa and the importance of IGFBP-4 and IGFBP-2 in regulation of IGF-II action within the follicle during its developmental pathway as an E2- or A-dominant follicle. In the androgen-treated female-to-male transsexual (TSX) model for PCOS, IGF-I, IGF-II, IGFBP-3 and IGFBP-1 levels do not differ.

Female↗
PubMed1995

Catecholamines in steroid-dependent brain development.

UNLABELLED: Sex-specific peculiarities of catecholamine (CA) content and turnover in neuroendocrine brain areas and their modification with neonatal steroids or prenatal stress (PS) in Wistar rats were studied. No changes in noradrenaline (NA) content and turnover rate were found in the preoptic area (POA), meanwhile dopamine (DA) turnover rates in the POA and mediobasal hypothalamus (MBH) were increased in neonatally androgenized 10-day-old females. Treatment of female neonates with various catecholestrogens increased hypothalamic NA content by 30-95% but only 4-hydroxyestradiol-17 beta induced anovulation. 6-Hydroxydopamine had no significant impact on hypothalamic CA content in neonates and did not prevent testosterone-induced persistent estrous. Maternal stress (restriction for 1 h a day, 15-21st days of pregnancy) resulted in a decrease of hypothalamic NA and blood plasma corticosterone response to acute stress in adult male offspring. Sex differences in CA content in the POA and MBH disappeared in 10-day-old prenatally stressed rats. CONCLUSIONS: (1) sexual brain differentiation needs co-operative actions of sex steroids and CA to be completed; and (2) early changes in CA content and turnover induced by PS or neonatal steroid exposure predetermine long-term alterations of the stress responsiveness, reproductive behaviour and neuroendocrine control of ovulation.

Animals↗
PubMed1995

Sex hormone-binding globulin and female reproductive function.

Although sex steroids have long been known to influence serum concentrations of SHBG, it is now recognized that nutritional factors may be more important in the regulation of SHBG in women. Thus, SHBG concentrations are negatively correlated with body mass index (BMI) and, more particularly, to indices of central adiposity. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is associated with truncal obesity, hyperandrogenism and hyperinsulinaemia. There is evidence that insulin may be the humoral mediator of the weight-dependent changes in SHBG. Serum SHBG concentrations are inversely correlated with both fasting and glucose-stimulated insulin levels, and insulin has been shown to have a direct inhibitory effect on SHBG synthesis and secretion by hepatocytes in culture. However, the interrelationship of BMI, insulin and SHBG appears to be different in women with PCOS from that in normal subjects. The clinical importance of the weight-related suppression of SHBG is illustrated by the finding of a greater prevalence of hirsutism in obese women PCOS compared with their lean counterparts. Obese subjects with PCOS have similar total testosterone concentrations to lean PCO women but have lower SHBG and reciprocally higher free testosterone levels. Calorie restriction results in reduction of serum insulin followed by an increase in SHBG and a fall in free testosterone but an isocaloric, low-fat diet has no significant effect on SHBG concentrations. Weight reduction in obese, hyperandrogenaemic women with PCO is an important approach to the management of both anovulation and hirsutism.

Diet↗