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Effects of fasting on neuroendocrine function and follicle development in lean women.

A 72-h fast in normal weight women during the follicular phase results in transient alterations in neuroendocrine function, but follicle development and follicular phase length remain unaltered. In this study we evaluated neuroendocrine and ovulatory function in lean women (body fat, < or = 20%) undergoing a similar 72-h fast. Compared to fed controls, fasted lean women experienced significant weight loss, blunting of the diurnal variation of cortisol, suppression of the nocturnal TSH rise, and a decrease in T3 levels after a 72-h fast. In contrast to similarly fasted, normal weight women, lean women have significantly higher evening cortisol levels and do not exhibit a normal nocturnal TSH rise after the fast. Lean fasted women exhibited a 19% decrease in the number of LH pulses over 24 h compared to fed women (12.9 +/- 1.3 vs. 16.0 +/- 1.9; P < 0.05). Fasting did not result in significant differences in mean LH, LH amplitude, LH area under the curve, and mean FSH levels in these lean women. Of the seven fasted cycles, two were anovulatory. In the five women studied in fed and fasted cycles, one had interrupted lead follicle development with anovulation, and four had significant lengthening of the follicular phase compared to those during their fed cycles (14.4 +/- 1.2 vs. 13.2 +/- 1.0 days; P = 0.01). The clinical observations made in this small sample of lean women showing more profound changes in neuroendocrine function, anovulation, and lengthened follicular phase after fasting suggest that lean women may be more vulnerable to fasting stress than normal weight women.

Absorptiometry, Photon↗

Mid-follicular phase pulses of inhibin B are absent in polycystic ovarian syndrome and are initiated by successful laparoscopic ovarian diathermy: a possible mechanism regulating emergence of the dominant follicle.

The hypothalamic pulse generator of GnRH is recognized to be central to ovulatory function as evidenced by the anovulation of women with hypogonadotrophic hypogonadism due to Kallmann's syndrome or severe anorexia nervosa. LH is released from the anterior pituitary in pulses, the frequency of which is closely entrained with those of GnRH. In contrast, secretion of FSH is influenced by a number of regulatory molecules, including GnRH, estradiol, inhibin, and activin. The close temporal relationship between changes in levels of inhibin B and FSH in the mid-follicular phase suggests that the release of inhibin B by the preovulatory follicle critically regulates pituitary FSH secretion. Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting ovulation, and abnormal ovarian morphology as detected by ultrasonography remains the most sensitive diagnostic marker for this disorder. The etiology of PCOS is unclear, but its effective treatment by both anti-estrogens and by exogenous FSH suggests that a primary disorder of FSH regulation may be central. To investigate the possible role of inhibin B in the pathology of PCOS, serum inhibin B levels were measured in 10 women with PCOS on cycle day 5 of a spontaneous or progestrogen-provoked bleed and compared with levels on cycle day 5 of 10 women with regular ovulatory cycles. The mean serum inhibin B levels in the PCOS patients were significantly higher at 248 (+/- 43.4) pg/mL compared with normal controls, 126 (+/- 18.6) pg/mL (P < 0.01). Ten women with clomiphene resistant PCOS and 5 normal controls consented to undergo serial blood sampling on cycle day 5. Time Series Analysis using a Fourier Transformation to analyze the power spectrum of the data revealed that in normal women there is a distinct periodicity in inhibin B levels with a clear peak detectable every 60-70 min (P < 0.05), whereas in women with ovulatory dysfunction due to PCOS, no such pattern of regular pulsatility was seen. Four women with PCOS whose anovulation was successfully treated with laparoscopic ovarian diathermy (LOD) underwent repeat venous sampling following LOD. Their serum inhibin B levels fell to the upper limit of the normal range (160 +/- 38.5) pg/mL, and pulsatility was initiated. It is possible that inhibin B pulses are being generated directly by the ovary in response to pulses of GnRH in the peripheral circulation, or indirectly in response to FSH pulses arising in the pituitary. The function of inhibin B pulses in the mid-follicular phase of the normal cycle remains to be elucidated, but the absence of the normal pulsatile pattern in women with PCOS, in conjunction with high basal levels of inhibin B arising from the multiple small follicles characteristic of the PCOS ovary, appears to reinforce the development of a large cohort of small, developmentally arrested, and ultimately atretic follicles in these patients. Initiation of normal inhibin B pulsatility by LOD in patients with polycystic ovaries appears to correlate with the post-operative onset of ovular cycles.

Diathermy↗

Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology.

Chronically elevated luteinizing hormone (LH) induces significant pathology in the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha (alpha)-subunit promoter to direct transgene expression specifically to gonadotropes in the anterior pituitary. Previously, it was shown that female LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors, and undergo precocious puberty from elevated LH and steroid hormones that fail to completely repress the alpha-subunit promoter. This chapter will discuss recent studies that further elucidate the impact of chronically elevated LH on diverse physiological systems. Granulosa cell tumors induced by elevated LH are strain dependent and prevented when transgenics are treated with human chorionic gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is generated, revealing several possible gene candidates for ovarian granulosa cell tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and oocytes exhibit increased rates of meiotic segregation defects, although meiotic competency is acquired normally. Anovulation can be rescued in transgenics by superovulation, though pregnancy fails at midgestation due to maternal factors. Uterine receptivity defects prevent implantation of normal embryos following induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical hyperfunction with increased corticosterone production following induction of adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the gonads and the adrenal gland, when expressed in conjunction with the inhibin-alpha SV40 transgene. Finally, chronic elevated LH promotes mammary tumorigenesis. The understanding of multiple clinical pathologies--including ovarian cancer, perimenopausal reproductive aging, premature ovarian failure, polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be enhanced through further study of this useful transgenic mouse model.

Aging↗

Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a.

In recent years, mammalian oocytes have been proposed to have important roles in the orchestration of ovarian follicular development and fertility. To determine whether intra-oocyte Foxo3a, a component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, influences follicular development and female fertility, a transgenic mouse model was generated with constitutively active Foxo3a expressed in oocytes. We found that the female transgenic mice were infertile, which was caused by retarded oocyte growth and follicular development, and anovulation. Further mechanistic studies revealed that the constitutively active Foxo3a in oocytes caused a dramatic reduction in the expression of bone morphogenic protein 15 (Bmp15), connexin 37 and connexin 43, which are important molecules for the establishment of paracrine and gap junction communications in follicles. Foxo3a was also found to facilitate the nuclear localization of p27(kip1) in oocytes, a cyclin-dependent kinase (Cdk) inhibitor that may serve to inhibit oocyte growth. The results from the current study indicate that Foxo3a is an important intra-oocyte signaling molecule that negatively regulates oocyte growth and follicular development. Our study may therefore give some insight into oocyte-borne genetic aberrations that cause defects in follicular development and anovulation in human diseases, such as premature ovarian failure.

Animals↗

Effect of sulpiride-induced hyperprolactinaemia on catecholamine turnover and LRH concentration in the medial basal hypothalamus of rats.

In order to clarify the mechanism of hyperprolactinaemic anovulation, the medial basal hypothalamic (MBH) catecholamine (CA) turnover and LRH concentration, and the serum levels and pituitary contents of gonadotrophins and prolactin (Prl) in hyperprolactinaemic female rats were examined. Hyperprolactinaemia (HPrl) was produced by oral administration of sulpiride for 10 consecutive days; each measurement made on the sulpiride-treated rats was compared with that of control dioestrus rats. Prl, LH, FSH and LRH were determined by radioimmunoassay; CA turnover, as assessed by the accumulation of CA following monoamine oxidase inhibition, was assayed by high performance liquid chromatography with electrochemical detection. Sulpiride treatment induced (1) an increase in the serum Prl and a decrease in the serum LH, (2) an increase in the pituitary FSH and LH contents, (3) an increase in the MBH LRH concentration, and (4) an increase in the MBH dopamine (DA) turnover. These results suggest that HPrl may induce anovulation by impaired LH secretion which was caused by the suppression of LRH release due to an increase in DA turnover in the MBH.

Animals↗

Decrease of LRH receptors in the pituitary gland in streptozotocin-induced diabetic rats.

In studies into the mechanism of anovulation in the diabetic condition, the LRH receptor content of the pituitary gland of rats with diabetes mellitus was determined. Normal female rats weighing 180-200 g were injected iv with either streptozotocin (6 mg/100 g body weight) or vehicle in dioestrus of the oestrous cycle. The rats were sacrificed by decapitation 9 days after treatment, and serum LH concentrations and the LRH content of the medial basal hypothalamus (MBH) were measured by radioimmunoassay (RIA), and the LRH receptor content of the pituitary gland was determined. The serum concentration of LH and the LRH content of the MBH in diabetic rats were 34.4 +/- 4.8 ng/ml (mean +/- SEM) and 2.05 +/- 0.04 ng/MBH, respectively, which were similar to the respective values of normal rats in dioestrus. However, the LRH receptor content of diabetic rats (13.2 +/- 3.9 fmol/pituitary) was significantly (P less than 0.05) lower than that of normal rats in dioestrus (68.0 +/- 7.1 fmol/pituitary) and pro-oestrus (59.4 +/- 13.6 fmol/pituitary). These results suggest that anovulation in diabetic rats is at least partly attributable to a low content of LRH receptors in the pituitary gland.

Animals↗

Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia.

OBJECTIVE: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. METHODS: The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. RESULTS: The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. CONCLUSIONS: We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.

Adolescent↗

Pharmacokinetic interactions between theophylline and other medication (Part I).

Many drugs have been found to increase or decrease the clearance of theophylline, probably by interaction with one or more of the variants of the cytochrome P450 drug-metabolising system. Theophylline may be particularly susceptible to alteration of its clearance because of the particular form(s) of the P450 system involved, because its metabolism is saturable, and/or because 90% of its elimination is via metabolism. Its clearance has been found to be decreased (typically by around 25%, but often by far more) by erythromycin, troleandomycin (triacetyloleandomycin), roxithromycin, enoxacin, ciprofloxacin, pefloxacin, norfloxacin, ofloxacin, fluoroquinolone T-3262, pipemidic acid, cimetidine, etintidine, propranolol, verapamil, diltiazem, nifedipine, furosemide (frusemide), at least some anovulent agents, viloxazine, allopurinol, ticlopidine, idrocilamide, thiabendazole, disulfiram, influenza- and BCG-vaccination, interferon, and caffeine (half-life increase). In contrast, theophylline clearance (clearance/bioavailability) was found to be increased by isoprenaline (isoproterenol), terbutaline, some corticosteroids, phenytoin, phenobarbital, activated charcoal, felodipine moricizine, benzodiazepines and sulfinpyrazone - typically by about 25%, but sometimes by as much as 80% or more. For several of these concomitant medications, however, only some of the published studies can substantiate an influence, which may highlight the sensitivity of some interactions to particular experimental and/or clinical conditions, e.g. with terbutaline, erythromycin, ciprofloxacin, norfloxacin, ofloxacin, phenobarbital, cimetidine, verapamil, diltiazem, nifedipine, anovulents, allopurinol and influenza vaccination. Moreover, reports both of inhibition and of induction of theophylline clearance by each of rifampicin and isoniazid have appeared. Nevertheless, under investigation many medications have not been found to perceptibly influence theophylline disposition kinetics, e.g. ephedrine, orciprenaline (metaproterenol), prednisone, prednisolone, temelastine, terfenadine, mequitazine, picumast, repirinast, josamycin, midecamycin, miocamycin, spiramycin, amoxicillin, ampicillin, cefalexin, cefaclor, ceftibuten, cotrimoxazole (trimethoprim plus sulfamethoxazole), tetracycline, doxycycline, lomefloxacin, fluoroquinolones NY-198 and AM-833, nalidixic acid, lincomycin, metronidazole, certain antacids, ranitidine, roxatidine, pirenzepine, rioprostil, metoclopramide, metoprolol, atenolol, nadolol, medroxyprogesterone, dextropropoxyphene (propoxyphene), piroxicam, ozagrel, mebendazole and ascorbic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

Immunohistochemical detection of plasminogen activator inhibitor-1 in polycystic ovaries.

Anovulation in women with polycystic ovary syndrome (PCOS) is incompletely understood. The concentration of the glycoprotein plasminogen activator inhibitor-1 (PAI-1) is raised in insulin resistance. This has been described in the granulosa and theca cell layers of the animal but not the human ovary. This study was performed to investigate the location of PAI-1 in the human ovary and investigate whether it may contribute to anovulation in PCOS. PAI-1 was localized immunohistochemically and quantitated using computer image analysis in 17 ovarian follicles from five women with a diagnosis of PCOS and compared with 15 follicles from six normal ovaries. PAI-1 was predominantly found in the granulosa and theca cells in both polycystic and normal ovaries. Image analysis did not reveal a difference in the PAI-1 signal from polycystic compared with normal ovaries. This study shows that PAI-1 plays a role in human ovulation, but its role in PCOS requires further research.

Adolescent↗

Genetic analysis of postpartum measures of luteal activity in dairy cows.

The objective of this study was to estimate genetic parameters for measures of luteal activity during the first 60 d postpartum. Analyses were made with different sampling intervals to investigate the possibility of combining progesterone measurement with routinely performed milk recording. Progesterone level in milk as an indicator of female fertility when selecting sires in a progeny-testing scheme was also examined. Data were collected from 1996 to 1999, and comprised 1,212 lactations from 1,080 British Holstein-Friesian cows at 8 commercial dairy farms in the United Kingdom. Milk samples for progesterone analysis were collected thrice weekly. Mixed linear animal models were used to analyze the data. Heritability for the percentage of samples with luteal activity during the first 60 d postpartum (PLA) was 0.30 and decreased with more infrequent sampling to 0.25, 0.20, and 0.14 for weekly, twice-monthly, and monthly sampling, respectively. Measures of PLA had a high negative genetic correlation with prolonged anovulation (-0.53 for monthly sampling, < -0.87 otherwise) and a moderate positive genetic correlation with persistent corpus luteum in the first estrus cycle (>0.65 if at least twice-monthly sampling). Genetic correlations with interval from calving to commencement of luteal activity were close to -1 for all PLA measurements and the selection index calculations showed that monthly progesterone sampling could be used with high accuracy (0.80 with 50 daughters per bull) to predict breeding values for commencement of luteal activity. Progesterone analysis at the time of regular milk recording could thereby be used to select for an early interval from calving to commencement of luteal activity and, at the same time, a decreased frequency of prolonged anovulation during the postpartum period.

Animals↗

Metabolic status and interval to first ovulation in postpartum dairy cows.

For 21 postpartum dairy cows studied during the period of negative energy balance, the rate of muscle protein degradation, gluconeogenic changes, circulating large neutral AA, and plasma IGF-I were measured to investigate their possible association with the duration of anovulation and LH secretions. Cows that ovulated (n = 17) were energetically deficient at first ovulation but were approaching a balanced state. The dynamic changes in energy balance, but not the mean energy balance or the extent of BW loss, were correlated with days to first ovulation. Variations in energy balance were explained largely by variations in energy intake. Increased mobilization of body protein was indicated by higher concentrations of 3-methylhistidine during the first 3 wk postpartum and was not correlated with duration of postpartum anovulation. Plasma aspartate transaminase decreased significantly, and the proportion of Tyr to total large neutral AA significantly increased in the 12 d prior to first ovulation; both were correlated with LH secretion. Plasma IGF-I did not correlate with days to first ovulation, but correlated with LH pulse frequency. These findings indicate that decreased gluconeogenesis from AA is associated with duration of recovery and that Tyr may participate in metabolic signaling to the hypothalamus-hypophyseal axis controlling ovarian function in the postpartum dairy cow.

Amino Acids↗

[Physiopathology of polycystic ovary syndrome].

The Polycystic Ovary Syndrome (PCOS) includes three phenotypic compartments, not always fully associated, consisting in hyperandrogenism, anovulation and metabolic syndrome, secondary to insulin resistance. The pathophysiological grounds lie upon two main components, i.e.: the theca-interstitial cell (TIC) and the granulosa cell (GC) dysregulations, the former accounting for hyperandrogenism and the latter for anovulation, and both of them being under the influence of hyperinsulinism. The former mainly results from an enzymatic overactivity, yielding an exaggerated output of androgens by the TIC, but the type(s) of enzymes as well as the genetic or adaptative nature of its (their) dysregulation are still controversial. The main consequence of the CG dysregulation is the follicular arrest just before the time of dominance. This might result from an intrinsic abnormality in CG, involving the IGFs and/or the Inhibin/Activin/Follistatin systems. Alternatively, the CTI might have deleterious effects on GC, mainly via the intra-ovarian hyperandrogenism. The latter should not be regarded any more as an atretogenic phenomenon. It is closely related to the two main morphological features of PCOS, i.e.: the stromal hyperplasia and the excessive follicular number.

Female↗

Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist in a low dose regimen.

BACKGROUND: GnRH agonists constitute a well-documented treatment for premenstrual syndrome (PMS). However, the hypo-estrogenic state induced by the treatment renders it less suitable for long-term clinical use. The aim of the current study was to investigate the efficacy of a low dose GnRH agonist with respect to its ability to relieve premenstrual symptoms and maintain regular ovulatory cycles. METHODS: The effect of a low dose GnRH agonist (buserelin) on luteal phase symptomatology was evaluated in 27 women with severe premenstrual syndrome. The design was doubleblind, placebo-controlled and cross-over. Patients were randomized to either GnRH-agonist intranasally in a dosage of 100 microg once daily for two months or placebo for two months before the cross-over was made. The primary outcome measure consisted of daily symptom ratings for mood and physical symptoms made by the patients throughout the study. Adverse events and hormone concentrations were assessed at visits every second week. RESULTS: Premenstrual irritability and depression were significantly relieved by low dose GnRH agonist. Positive symptoms such as friendliness and cheerfulness were also improved during the premenstrual week. Likewise physical symptoms of swelling and headache displayed a significant improvement during buserelin treatment, whereas breast tenderness scores were unaffected by the treatment. The low dose GnRH agonist treatment regimen induced anovulation in as much as 56% of patients, but these subjects were significantly older than those women who maintained ovulatory cycles throughout the study. CONCLUSION: GnRH treatment significantly reduced premenstrual depression and irritability. However, low dose GnRH therapy is prone to induce anovulation, particularly with increasing age.

Adult↗

Precocious pubarche in girls and the development of androgen excess.

The prevalence of ovarian hyperandrogenism, hyperinsulinism and dyslipidemia is increased among adolescent girls with a history of premature pubarche (defined as the appearance of pubic hair before the age of 8 yr). The ovarian hyperandrogenism is characterized by clinical signs of androgen excess and by an exaggerated ovarian 17-hydroxyprogesterone response to GnRH agonist stimulation. The hyperinsulinism and dyslipidemia are detectable before and during pubertal development, and are commonly accompanied by low serum levels of insulin-like growth factor binding-protein 1 (IGFBP-1) and sex hormone-binding globulin (SHBG), and by an increased prevalence of anovulation from late adolescence onwards, even in the absence of clinical signs of androgen excess. In girls, premature pubarche, hyperinsulinism, low IGFBP-1, dyslipidemia, anovulation and hyperandrogenism--and some combinations of these--have been related to reduced fetal growth, indicating that these constellations or sequences may have a prenatal origin. Together, these findings suggest that premature pubarche in girls should no longer be merely regarded as a normal variant of development, but rather as a childhood marker pointing to an increased risk for a polyendocrine-metabolic disorder of prenatal origin.

Female↗

[Study on relationship between ovulation inducing effect of drug-acupuncture and endometrial contents of estradiol receptor and progesterone receptor].

OBJECTIVE: To study the effect of Chinese herbal medicine for replenishing Kidney combined with acupuncture in treating anovulation and infertility, and the relationship between its ovulation inducing effect and endometrial contents of estradiol receptor (ER) and progesterone receptor (PR). METHODS: Twenty-nine cases were treated with replenishing Kidney drugs combined with acupuncture for 1-3 months. Patients' ER and PR were measured by immunohistochemical method. And patients were classified according to PR content into PR positive group and mild PR positive group. RESULTS: Fifteen cases of PR positive group, completed treatment for 45 cycles, among them, 40 cycles showed ovulation, the ovulation rate being 88.89%. Ten in 14 cases, who complicated with infertility, became pregnant, the pregnant rate being 71.43%. While in 11 cases of PR mild positive group, 9 complicated with infertility, completed treatment for 33 cycle, 10 cycles showed ovulation (30.30%), and pregnant rate 22.22% (2/9). The difference between the two groups was significant (P < 0.01). CONCLUSION: The replenishing Kidney drugs combined with acupuncture treatment could result a good effect in treating infertility due to anovulation, especially on those with high endometrial PR content.

Acupuncture Therapy↗

Current perspectives in polycystic ovary syndrome.

Polycystic ovary syndrome has been viewed primarily as a gynecologic disorder requiring medical intervention to control irregular bleeding, relieve chronic anovulation, and facilitate pregnancy. A large body of evidence has demonstrated an association between insulin resistance and polycystic ovary syndrome. The former condition has an established link with long-term macrovascular diseases such as type 2 diabetes mellitus, hypertension, and atherosclerotic heart disease, consequences that also are observed in women with polycystic ovary syndrome. In addition, chronic anovulation predisposes women to endometrial hyperplasia and carcinoma. The purpose of this review is to examine the clinical course of this syndrome, which spans adolescence through menopause, and suggest a simple and cost-effective diagnostic evaluation to screen the large numbers of women who may be affected. Therapy, which should be individualized, should incorporate steroid hormones, antiandrogens, and insulin-sensitizing agents. Weight loss by way of reduced carbohydrate intake and gentle exercise is the most important intervention; this step alone can restore menstrual cyclicity and fertility, and provide long-term prevention against diabetes and heart disease. Treatment alternatives should be directed initially toward the most compelling symptom. Longitudinal care is of paramount importance to provide protection from long-term sequelae.

Female↗

Psychological aspects of infertility due to various causes--prospective study.

SUBJECTS AND METHODS: One hundred and twenty infertile couples (30 each among unexplained infertility, anovulation, tubal factor, and male factor groups) and 30 fertile couples as controls were evaluated for psychological assessment by different psychological test instruments. Initial evaluation was done at recruitment, followed by reassessment at 3, 6, 9 and 12 months during the infertility work-up, and at the end when the specific diagnosis and the management and prognosis were disclosed. RESULTS: Psychological components were found to play a significant role in infertility of unknown etiology, especially in the male partner. They affected the personality and social behavior of the male partner and caused anxiety, but led to depression in the female partner. In cases of organically caused infertility, partners were worried about the other's reaction. Anxiety was significantly greater in the partner with the fertility problem than in the other partner. Life events were significant in the partner in whom the fertility problem was detected. Periodic psychological assessment was not affected by infertility work-up on the male partner in any of the groups, whereas anovulation and tubal factor infertility showed a significant psychological effect on the female partner at the end of work-up. Depression and anxiety in the female partner were evident soon after the investigation started.

Adaptation, Psychological↗

Ovulation stimulation and induction.

Evaluation of gonadotropins, prolactin, and thyroid function in anovulatory women directs subsequent therapy. Treatment should be initiated with the agent that is the safest and least costly for the specific indication. Except in cases of FSH elevation, pregnancy rates should approximate those of normally ovulating women. Bromocriptine, the drug of choice for hyperprolactinemia, restores ovulation in greater than 90% of women treated. Clomiphene citrate remains the drug of choice for normoestrogenic anovulation. Although drug-resistant women may respond to extended regimens, failure to ovulate or to conceive within six ovulatory cycles with clomiphene is an indication for menotropin therapy. Menotropins and pulsatile GnRH should be considered first line therapy for women with hypogonadotropic anovulation. When using hMG or pulsatile GnRH in clomiphene-resistant patients, pretreatment with GnRH analogs may normalize their response and result in higher pregnancy rates. GnRH analogs prevent premature luteinization in hMG-induced in vitro fertilization and gamete intrafallopian transfer cycles, resulting in lower cancellation rates and improved oocyte quality. Superovulation with clomiphene citrate should be attempted in patients with unexplained infertility prior to using menotropin therapy.

Bromocriptine↗