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Prolonged postpartum anovulation in mastectomized cows requires tactile stimulation by the calf.

Association of the calf with its dam prolongs the postpartum interval to first ovulation in intact and mastectomized cows indicating that tactile stimulus of the teat and (or) udder is not necessary. Therefore, we conducted the following experiment to determine whether individual calves allowed restricted contact with their mastectomized dam would delay the onset of first postpartum ovulation. Mastectomized cows (n = 21) were allotted randomly and equally to three groups in which cows were 1) allowed unrestricted access to their calves, with unlimited tactile, olfactory, visual, and auditory stimuli (calf present); 2) removed permanently from their calves 24 h after parturition and provided no further association with their calves (calf removed); and 3) remained with their calves for 24 h and then the cow-calf pair was restricted to a pen where tactile contact of the calf was limited to the head and neck region of its dam (calf restricted). Seven udder-intact cows (control) remained with their calves and were allowed to nurse ad libitum. Postpartum intervals to ovulation and first estrus for the calf-restricted cows and calf-removed cows were similar but shorter (P < .05) than those for the calf-present and udder-intact groups. We conclude that restricting tactile stimuli of the calf to the head and neck area of its dam failed to prolong postpartum anovulation in the mastectomized dam and that a cow-calf nursing orientation with tactile stimuli to the inguinal area, but not limited to the teat and(or) udder, was sufficient to prolong anovulation.

Animals↗

Laparoscopic surgery of chronic hyperandrogenic anovulation.

The review describes briefly the clinical and endocrinological characteristics of chronic hyperandrogenic anovulation (CHA), as well as ovulation induction by hormone therapy (therapy of first choice) and by classical wedge resection. The main purpose of this study, however, is to compare different laparoscopic treatments of CHA, with emphasis on laser treatments by argon, CO2, Nd:YAG, and frequency-doubled Nd:YAG laser. The overall results of laparoscopic treatments in hormone-therapy-resistant patients with CHA are encouraging and the results are comparable. In the studies considered in this review, ovulation was induced for longer or shorter periods in 21 out of 31 patients (68%) after ovarian biopsy, in 57 out of 73 patients (78%) after electrosurgery, and in 82 out of 118 patients (70%) after laser treatment. Subsequent conception occurred in 44%, 40%, and in 41% of the patients, respectively. Of interest is the fact that some hormone-therapy-resistant patients become sensitive to Clomiphene after laparoscopic treatment, giving an overall percentage of ovulation and an overall pregnancy rate of 89% and 54%, respectively, for electrosurgery, and of 88% and 50%, respectively, for laser treatment. Unfortunately, adhesion formation, a serious complication of surgical treatment of the ovaries, is still a drawback using laparoscopic surgical techniques.

Anovulation↗

Anovulation, inadequate luteal phase and poor sperm penetration in cervical mucus during prolonged use of Norplant implants.

Blood samples for progesterone assay were collected for a total of 49 cycles, from 27 volunteers using the NORPLANT system. Levonorgestrel determinations were carried out in the same samples. A group of 12 women with normal cycles were studied in the same manner to serve as controls. Of the 49 cycles studied, 20 (41%) were ovulatory. The mean levonorgestrel level in ovulatory patients was 0.34 +/- 0.11 ng/ml (S.D.) compared to 0.42 +/- 0.14 ng/ml (S.D.) in anovulatory cycles. Compared to the control group, progesterone levels were significantly lower for users of NORPLANT implants during days -12 to -10 (p less than 0.025), -9 to -7 (p less than 0.05), -6 to -4 (p less than 0.0005) and days -3 to -1 (p less than 0.01). Cervical mucus evaluations and post-coital tests were done around mid-cycle in 29 of the cycles studied. All samples of cervical mucus were of poor quality, viscous and scarce, with a mean SPK of 4.1 +/- 2.3 cm. Most had absent or atypical ferning. Twenty-one subjects (73%) had a post-coital score of 1, and 4 (14%) of zero. Thus, anovulation, inadequate luteal phase and the direct effect of the continuous administration of levonorgestrel over cervical function, all seem to contribute to the effectiveness of NORPLANT implants.

Anovulation↗

Ovarian interstitial YAG-laser: an effective new method to manage anovulation in women with polycystic ovary syndrome.

OBJECTIVE: This study was undertaken to assess the effectiveness of transvaginal ultrasound-guided ovarian interstitial laser-coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Nineteen anovulatory women with clomiphene citrate-resistant PCOS underwent ultrasound-guided transvaginal ovarian interstitial YAG-laser treatment. In this study, serum hormonal level, spontaneous ovulation rate, and pregnancy rate were assessed. RESULTS: With a spontaneous ovulation rate of 84.2%, 16 of 19 cases ovulated regularly during the 6-month postoperative period. The mean serums luteinizing hormone and serum testosterone levels in the second, fourth, and sixth postoperative months were significantly lower than preoperative levels: 5.87 +/- 2.04 IU/L versus 13.17 +/- 3.03 IU/L (P < .001) and 2.98 +/- 1.79 nmol/L versus 5.49 +/- 3.23 nmol/L (P < .001), respectively. The mean luteinizing hormone/follicle-stimulating hormone ratio was also significantly lower postoperatively at 1.09 +/- 0.30 compared with the preoperative 2.85 +/- 1.14 (P < .001). There was a cumulative pregnancy rate at 6 months of 32.3% (6/19) among the subjects. No significant operative complications were encountered. CONCLUSION: The ultrasound-guided transvaginal ovarian interstitial laser treatment may be an effective new method to manage anovulation in PCOS patients.

Adult↗

Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus.

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. Recent prevalence estimates suggest that 5-10% of premenopausal women have the full-blown syndrome of hyperandrogenism, chronic anovulation, and polycystic ovaries. Evidence suggests that women with polycystic ovary syndrome have a unique disorder of insulin action and are at increased risk to develop non-insulin-dependent diabetes mellitus. Further, non-insulin-dependent diabetes mellitus in women with polycystic ovary syndrome has a substantially earlier age of onset (third to fourth decades) than it does in the general population (sixth to seventh decades). Studies assessing whether abnormalities in insulin action are intrinsic or secondary to the hormonal milieu have found that insulin-induced receptor autophosphorylation is markedly diminished in approximately 50% of polycystic ovary syndrome women. This defect is unique to women with polycystic ovary syndrome and is not seen in other common insulin-resistant states of obesity and non-insulin-dependent diabetes mellitus. In polycystic ovary syndrome women who have normal receptor autophosphorylation, it remains likely that signaling mechanisms downstream of the receptor are abnormal, since these women are also insulin resistant. This distinctive post-insulin-binding defect appears to be genetic, since it is present in cells removed from the in vivo environment for generations.

Anovulation↗

Role of androgenic hyperactivity in anovulation.

In the course of an investigation of 60 patients with clomiphene-resistant anovulation, 35 cases of androgenic hyperacitvity were detected. Fractionation of urinary 17-ketosteroids (17-KS) by a rapid method of chromatography proved to be both practical and reliable for the detection and classification of androgenic disorders of adrenal, ovarian, or mixed origin. In contrast to the total 17-KS values, the fractionated 17-KS values were elevated in all but one of these cases. Following dexamethasone suppression, individual 17-KS showed significant decreases in both adrenal and mixed adrenal-ovarian cases, in contrast to ovarian cases in which no significant change was detected. Human chorionic gonadotropin (HCG) stimulation combined with dexamethasone suppression did not cause any significant change in individual 17-KS values in the adrenal group, whereas both the mixed adrenal-ovarian and ovarian cases showed significant increases. Of 34 treated patients, 22 conceived, 21 had normal deliveries, and 1 aborted. Twelve became ovulatory. Eleven patients were treated with dexamethasone, nineteen with combined dexamethasone and clomiphene, two with dexamethasone and HCG, and two with HCG only.

17-Hydroxycorticosteroids↗

Progressive dosages of clomiphene in hypothalamic anovulation.

A group of 89 sterile patients with hypothalamic anovulation were subjected to progressive dosages of clomiphene citrate according to a predesigned program. In order to analyze our results, we divided our patients into seven groups, according to the largest dosage of clomiphene citrate received. Clinical features were revised in relation to the ovulatory dose of clomiphene. Significant differences between groups regarding weight, menstrual pattern, age at menarche, and hirsutism were not found. Obesity increased the dose required for ovulation when it was less than 900 mg/cycle, but had no effect at higher doses. The ovulation rate, pregnancies, prenatal wastage, and side effects of treatment were analyzed; and it was found that the scheme for ovulation induction used, without expensive and sophisticated ovarian monitoring resources, improved ovulation and pregnancy rates with few and unimportant deleterious side effects.

Anovulation↗

Luteinizing hormone bioactivity and variable responses to clomiphene citrate in chronic anovulation.

In 18 women with infertility and chronic anovulation with normal gonadotropins, three different responses were observed to increasing doses (250 to 750 mg) of clomiphene citrate (CC). Follicle development and ovulation in 8, follicle development but no ovulation without human chorionic gonadotropin (hCG) in 6, and no response to CC in 4. Serum concentrations of bioactive luteinizing hormone (bioactive-LH), immunoactive (immunoactive-LH), follicle-stimulating hormone, and estradiol (E2) were measured and follicle growth was assessed by daily ultrasound. Findings were compared with 8 normal ovulatory controls. Folliculogenesis on CC therapy, based on our data, was 78%; however, only 44% ovulated spontaneously, 34% required hCG for follicle rupture. There were no apparent hormonal indicators to predict responders from nonresponders. The absence of an LH surge in the presence of follicles and sustained high E2 concentrations in 34% of patients may be associated with a decreased E2 sensitivity at the hypothalamic-pituitary level. Ultrasound easily identified patients who responded to CC with folliculogenesis but did not initiate an LH surge. Follicle rupture was achieved promptly by hCG administration.

Adult↗

Treatment of chronic anovulation resistant to clomiphene citrate (CC) by using oral contraceptive ovarian suppression followed by repeat CC treatment.

OBJECTIVE: To evaluate the effectiveness of a 2-month oral contraceptive (OC) ovarian suppression followed by clomiphene citrate (CC) in patients who had failed to ovulate on maximum doses of CC alone. DESIGN: Prospective, nonrandomized observational study. SETTING: Private tertiary infertility center. PATIENT(S): Thirty-eight patients with documented anovulation by transvaginal ultrasound follicular monitoring while receiving CC in doses of 150 mg or higher. INTERVENTION(S): Two-month ovarian-hypothalamic-pituitary axis suppression with OCs followed by repeat CC 100 mg for 5 days. MAIN OUTCOME MEASURE(S): Follicle growth, endometrial development, and ovulation were confirmed by transvaginal ultrasound. Pregnancy was confirmed by serum hCG levels and 7-week gestation ultrasound. RESULT(S): Thirty-eight patients completed 95 treatment cycles. Twenty-nine patients became ovulatory (76%), and 69 of the 95 cycles were ovulatory (72.6%), resulting in 22 pregnancies in the 38 patients for a cumulative pregnancy rate of 58%. CONCLUSION(S): Suppression of the hypothalamic-pituitary-ovarian axis for 2 months with OCs followed by CC treatment results in excellent rates of ovulation and pregnancy in women who had previously failed to ovulate on CC alone. This treatment offers an effective, reasonable, inexpensive, and low-risk alternative before gonadotropin therapy.

Adult↗

Urinary follicle-stimulating hormone (FSH) versus recombinant FSH in clomiphene citrate-resistant, normogonadotropic,chronic anovulation: a prospective randomized study.

OBJECTIVE: To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation. DESIGN: Prospective, randomized trial. SETTING: University-based infertility clinic. PATIENT(S): Fifty-one women. INTERVENTION(S): Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken. MAIN OUTCOME MEASURE(S): Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate. RESULT(S): Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered. CONCLUSION(S): Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol.

Adult↗

Does anovulation exist in eumenorrheic women?

OBJECTIVE: To determine whether anovulation exists in normally menstruating women. METHODS: In a database of 550 consecutive couples seeking pregnancy, results of the midluteal serum progesterone level analysis planned for 7 days before the onset of the next menses were examined in women with predictable cycles shorter than 35 days. RESULTS: Of the 550 couples seeking pregnancy, 410 of the female partners (74.5%) were eumenorrheic. Fifteen of these women (3.7%) had apparently anovulatory cycles with a progesterone lower than the normal ovulatory value of 15 nmol/L. Further examination showed that four of the 15 women (26.7%) had an isolated prolonged cycle, whereas an additional four (26.7%) failed to have their sample taken at an appropriate time. One (6.7%) had a low progesterone level that was normal in the subsequent cycle. Two patients (13.3%) were older than 40, both having elevated early follicular follicle-stimulating hormone levels. One patient (6.7%) conceived in the following menstrual cycle without further evaluation. The three remaining women (20%) showed consistently apparently anovulatory cycles. However, the levels were exclusively above the follicular range. CONCLUSION: Our findings cast doubt on the concept of anovulatory cycles in eumenorrheic women and suggest that further examination of the lower level of ovulatory progesterone may indeed be necessary.

Adult↗

The administration of cortisone to female B6A mice during their immune adaptive period causes anovulation and the formation of ovarian cysts.

PROBLEM: Female mice that are injected with estradiol-17beta (E2) and testosterone during the 7-day immune adaptive period are infertile at adulthood. To determine whether the resultant infertility can be caused by steroids other than estrogens/ androgens, this study examined the effect of injecting cortisone, alone, and in combination with E2 and testosterone, on reproductive function. METHOD OF STUDY: Neonatal (C57BL/6J x A/J)F1 B6A female mice were injected from 3 to 6 days of age with sesame oil:ethanol (9:1; v:v), alone, or containing 20 microgg cortisone acetate, 20 microg E2, or 20 microg testosterone. Two additional groups were given 20 microg cortisone acetate in combination with 20 microg E2 or 20 microg testosterone. At adulthood the animals were killed, the stage of vaginal estrus determined, the ovaries examined for the presence of corpora lutea and follicular cysts, and circulating levels of progesterone, E2, and testosterone were measured by radioimmunoassay (RIA). RESULTS: It was found that injections of cortisone seriously compromise reproductive development. For example, 11% of cortisone-injected animals had ovaries that lacked corpora lutea. In addition, 39% of cortisone-injected females had ovaries with follicular cysts. Cortisone-injected females also had low levels of circulating progesterone (18 ng/mL versus 30 ng/mL for the sesame oil-injected females). CONCLUSION: It is concluded that the deleterious effect of steroids on reproductive function, when administered during the immune adaptive period, is not restricted to estrogens and androgens. It is proposed that injections of cortisone alter T-lymphocyte subsets, which contributes to anovulation and the production of follicular cysts.

Animals↗

Pathophysiology of anovulation.

Anovulatory disorders are physiological during puberty, postpartum period and just before the menopause. In pathology, they are one of the earliest symptoms of different diseases: functional or organic hypothalamic diseases, pituitary destruction or inappropriate feedback by the peripheral hormones and, obviously, primary ovarian insufficiency. Their real interest lies in their pathophysiology. Functional hypothalamic disorders are defined as the inability to liberate GnRH in a physiological way. The role of endogenous opioids, as essential factors of gonadotrophin regulation will be discussed. Hyperprolactinaemias, which represent 20% of the anovulations, have an antigonadotrophic effect at the hypothalamic level, but the very mechanism of the inhibitory effect of prolactin on GnRH is still open to discussion. Although polycystic ovarian disease is one of the most common endocrine abnormalities in women, its pathophysiology remains far from fully understood. The relative parts played by hypothalamic disturbances and by abnormal feedback of gonadal steroids will be discussed.

Anovulation↗

The choice of treatment for anovulation associated with polycystic ovary syndrome following failure to conceive with clomiphene.

The choice of treatment for clomiphene-resistant anovulation associated with polycystic ovary syndrome (PCOS) is presently arbitrary and selection criteria are not available. A total of 144 women with anovulatory infertility associated with PCOS who failed to conceive on clomiphene were treated with either pure follicle stimulating hormone (FSH) (n = 29), or human menopausal gonadotrophin (HMG) (n = 60), or gonadotrophin-releasing hormone analogue (GnRHa) and HMG (n = 55). Analysis of 306 treatment cycles and 53 pregnancies revealed a cumulative conception rate at 4 months of 23% with FSH, 47% with HMG and 69% with GnRHa + HMG. The miscarriage rate was highest in the HMG group (44%) and consequently the cumulative live birth rate was superior when GnRHa was used in combination with HMG. There were no significant differences in the basal clinical and endocrinological features of those who conceived compared with those who did not, either in the whole group, or in the individual treatment groups. Thus, the choice of treatment for clomiphene-resistant women with PCOS cannot be guided by the basal clinical or endocrinological features of this heterogeneous syndrome with the present state or knowledge.

Adult↗

The effects of an aromatase inhibitor and a 5 alpha-reductase inhibitor upon the occurrence of polyovular follicles, persistent anovulation, and permanent vaginal stratification in mice treated neonatally with testosterone.

Female C57BL/Tw mice were given 5 daily injection of 20 micrograms testosterone (T), 100 micrograms 4-hydroxy-4-androstene-3, 17-dione (4-HA), 100 micrograms 6-methylene-4-pregnene-3, 20-dione (6-MP), 4-HA + 6-MP, T + 4-HA, T + 6-MP, and T + 4-HA + 6-MP starting on the day of birth. The animals were ovariectomized at 30 days or 90 days of age and were killed at 150 days. The incidence of polyovular follicles (PF) at 30 days of age was significantly increased by neonatal treatment with T. By contrast, the PF incidence was significantly reduced by injections of 4-HA given simultaneously with T. Neonatally T- or T + 6-MP-treated 90-day-old mice had ovaries containing follicles and hypertrophied interstitial cells but no corpora lutea. By contrast, T + 4-HA (64%)- and T + 4-HA + 6-MP (82%)-treated mice had ovaries with corpora lutea. In the T + 4-HA + 6-MP (82%)-treated mice had ovaries with corpora lutea. In the T + 4-HA + 6-MP-treated, 150-day-old, ovariectomized mice, the number of mice showing vaginal epithelial stratification was significantly decreased as compared with T-treated mice. There were no significant differences in the number of layers, thickness, and mitotic rate of vaginal epithelium of T-treated mice compared with mice treated with T + 4-HA, T + 6-MP, or T + 4-HA + 6-MP. The present results indicate that development of PF and persistent anovulation are due to the direct action of estrogen (E) derived from T upon neonatal ovarian follicles and the neonatal hypothalamo-hypophysial system, and that T itself can induce ovary-independent vaginal changes, although 5 alpha-reduced androgen and estrogen derived from T seem to be more effective in this regard.

5-alpha Reductase Inhibitors↗

Evidence for maternal behavior as a requisite link in suckling-mediated anovulation in cows.

Some component of the suckling process inhibits LH secretion and delays postpartum ovulation in beef cows. To investigate a possible role for maternal behavior in suckling-mediated anovulation, 27 crossbred beef cows were randomly allotted to 1 of 3 groups: 1) alien (dam suckled by alien calf; n = 11); 2) own (dam suckled by own calf; n = 8); and 3) weaned (calf removed for 6 days; n = 8). Beginning 14-17 days after parturition (experimental Day 0), cows were control suckled (10 min every 6 h) in stanchions for 6 days by either their own calf or by an alien calf or were weaned. Mean LH pulse frequencies in the alien and weaned groups were similar but were elevated (p < 0.02) on experimental Days 2 and 4 compared to those in the own group. The incidence of luteal activity by experimental Day 10 was greater (p < 0.01) for the alien (72.2%) and weaned groups (75.0%) than for the own group (12.5%). Frequency of oxytocin release following suckling was greater (p < 0.01) in the own group than in the alien group (Day 2: 100% vs. 36.4%; Day 4: 100% vs. 54.6%), whereas suckling-induced release of prolactin was similar for both groups. Data provide evidence that the mother-offspring bond is an important link in suckling-mediated inhibition of LH secretion and ovulation.

Aggression↗

The luteinized unruptured follicle syndrome: anovulation in disguise.

The luteinized unruptured follicle syndrome is a form of anovulation and a subtle cause of female infertility. The syndrome cannot be diagnosed by traditional progesterone-dependent ovulation detection methods. Without the use of invasive procedures or sophisticated equipment, the luteinized unruptured follicle syndrome may go unnoticed. The patient diagnosed as ovulatory, on the basis of traditional ovulation detection methods, who does not conceive may be experiencing the luteinized unruptured follicle syndrome, and thus infertility. The syndrome's incidence, detection, etiology, and treatment are described.

Adult↗

Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism.

Polycystic ovaries were defined with ultrasound imaging in a series of 173 women who presented to a gynaecological endocrine clinic with anovulation or hirsutism. Polycystic ovaries were found in 26% of women with amenorrhoea, 87% with oligomenorrhoea, and 92% with idiopathic hirsutism--that is, hirsutism but with regular menstrual cycles. Fewer than half the anovulatory patients with polycystic ovaries were hirsute, but in 93% of cases there was at least one endocrine abnormality to support the diagnosis of polycystic ovaries--that is, raised serum concentrations of luteinising hormone, raised luteinising hormone: follicle stimulating hormone ratio, or raised serum concentrations of testosterone or androstenedione. This study shows that polycystic ovaries, as defined by pelvic ultrasound, are very common in anovulatory women (57% of cases) and are not necessarily associated with hirsutism or a raised serum luteinising hormone concentration. Most women with hirsutism and regular menses have polycystic ovaries so that the term "idiopathic" hirsutism no longer seems appropriate.

Androstenedione↗