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Transvaginal hydrolaparoscopic ovarian drilling using bipolar electrosurgery to treat anovulatory women with polycystic ovary syndrome.

STUDY OBJECTIVE: To verify the value, feasibility, and reliability of transvaginal hydrolaparoscopic ovarian drilling using the bipolar VersaPoint system to treat clomiphene-resistant, anovulatory women with polycystic ovary syndrome. DESIGN: Prospective clinical study (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Twenty-eight women. INTERVENTION: Transvaginal hydrolaparoscopic ovarian drilling using the bipolar VersaPoint spring electrode. MEASUREMENTS AND MAIN RESULTS: After the surgical procedure, ovulation occurred spontaneously in 66.7% of women. Thirteen pregnancies occurred; eight were spontaneous, and four were achieved after induction of ovulation with clomiphene citrate and one after stimulation with gonadotropins. In 21 women whose infertility was due exclusively to anovulation, the cumulative pregnancy rate was 38% at 3 months and 76% at 6 months. No ovarian hyperstimulation or abortion occurred. The single complication was bleeding from an ovary that required conversion to laparoscopy. CONCLUSION: Transvaginal hydrolaparoscopic ovarian drilling with the bipolar VersaPoint system is a useful therapeutic option in these women.

Adult↗

Infertility in women: an update.

OBJECTIVE: To review pharmacologic therapy of infertility disorders in women. DATA SOURCES: Current clinical literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: The complex interplay of hormones and cells is the focus of most pharmacotherapeutic interventions in women with infertility problems. Treatment remains more of an art than a science at this time. Since the cause of infertility cannot be identified in many cases, practitioners use medications to overcome potential problems with anovulation, secondary ovarian failures, hypothalamic-pituitary dysfunction, and hyperprolactinemia. This article reviews the use of clomiphene, human chorionic gonadotropin, menotropins such as human menopausal gonadotropin and urofollitropin, gonadotropin-releasing hormone, and dopamine agonists. CONCLUSION: Although few pharmacists are closely involved in the treatment of women with infertility, they can be sources of information, monitor families for signs and symptoms of psychologic stress associated with treatments, and help patients with practical instructions.

Anovulation↗

The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes.

A randomized controlled trial of periconceptional multivitamin supplementation (including 0.8 mg folic acid--see the Materials and Methods section for the precise composition of the multivitamin and trace-element supplementation) was carried out for at least 28 days before conception. The trial was continued until at least until the second missed menstrual period to test the effectiveness of this new primary preventive method in the reduction of neural tube defects. However, other pregnancy outcomes were also evaluated. Of a total of 5,502 pregnant women, 4,846 births were analysed in the final data base. The rate of multiple births was significantly higher in the multivitamin group (3.8%) than in the placebo-like trace-element control group (2.7%), and in both groups exceeded the multiple birth rate of 2.2% in the Hungarian population at large. 7.3% of women in the multivitamin and 7.9% of women in the trace-element groups had received ovarian stimulation treatment (mainly clomiphene) for hormonal dysfunctions, eg. anovulation. Nonetheless, our study showed that periconceptional multivitamin supplementation, with or without ovarian stimulation, increases the rate of multiple births.

Abortion, Induced↗

The recovery of fertility during breast-feeding in Assiut, Egypt.

A longitudinal study of twenty-six breast-feeding and twelve non-breast-feeding postpartum women was conducted in Assiut, Egypt in order to determine the time that ovulation resumed after childbirth, and the effect of breast-feeding frequency on the period of lactational anovulation. Breast-feeding women experienced the onset of follicular development, vaginal bleeding, ovulation and pregnancy significantly later than women who did not breast-feed. Ovulatory and non-ovulatory breast-feeders reported similar frequencies of breast-feeding episodes. The introduction of dietary supplements commonly preceded ovulation. An algorithm using three simple variables observable to the breast-feeding mother was found to predict up to 100% of the first ovulations. All breast-feeding women who did not give supplements and did not have a vaginal bleeding episode by 6 months postpartum were anovular by strict criteria for ovulation. Ovulation did not precede bleeding or supplementation in the women who experienced these events before 6 months, yielding a highly effective formula for preventing unplanned pregnancy by the informed use of breast-feeding.

Adolescent↗

Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications.

The polycystic ovary syndrome (PCOS) is a prevalent disorder affecting approximately 6% of women of reproductive age, and is characterized by anovulation and hyperandrogenism. It has also become apparent that a frequent feature of women with PCOS is insulin resistance accompanied by compensatory hyperinsulinemia, and increasing evidence suggests that hyperinsulinemia plays an important role in the pathogenesis of PCOS. This article will review (1) evidence indicating that insulin contributes to the hyperandrogenism of PCOS by stimulating ovarian androgen production and decreasing serum sex hormone-binding globulin (SHBG) concentrations; (2) possible direct effects of hyperinsulinemia on folliculogenesis; (3) the relationship between insulin and adrenal androgens in women; and (4) therapeutic and clinical implications of these findings.

Adrenal Glands↗

Adrenal involvement in polycystic ovary syndrome.

The etiology of hyperandrogenic chronic anovulation is heterogeneous and relatively unknown in the majority of cases. Affected individuals in this latter segment are considered to have polycystic ovary syndrome (PCOS) of which 50 to 60% exhibit androgen excess of adrenal origin. An understanding of normal adrenal function provides insight into the factors that contribute to adrenal androgen excess in PCOS. Since pituitary ACTH secretion promotes developmental growth and overall steroidogenic efficiency within the adrenal cortex, it is probable that these actions of ACTH along with the adrenal's unique centripetal circulation play a major role in the induction of adrenarche. This latter phenomenon is characterized by alterations in adrenocortical morphology and steroidogenic enzyme activities culminating in increases in adrenal androgens to normal circulating adult levels. Thus, it is not surprising that adrenal dynamic testing has revealed increased 17,20 lyase activity or adrenal androgen hyper-responsiveness to ACTH as the two abnormalities leading to adrenal androgen excess in PCOS. Whereas 17,20 lyase hyperactivity diagnosed by defined criteria in response to pharmacological ACTH may be an intrinsic genetic defect, increases in 17,20 lyase activity and adrenal androgen hyper-responsiveness to ACTH in response to physiological ACTH may be promoted by the functional elevation of estrogen of ovarian origin in PCOS. The latest in vitro data suggest the estrogen may elicit its effect on the adrenal cortex through a receptor mediated mechanism. Therefore, the currently available data indicate that adrenal androgen excess in PCOS is also heterogeneous in etiology.

Adrenal Cortex↗

Metergoline and bromocriptine in the management of tumoral and idiopathic hyperprolactinemia.

59 patients affected by amenorrhea or anovulation, 37 of whom also with galactorrhea, and with hyperprolactinemia of unknown origin (idiopathic hyperprolactinemia, 24 patients) or due to a pituitary microadenoma (tumoral hyperprolactinemia, 35 patients) were treated with metergoline (4-12 mg/day) or with bromocriptine (2.5 to 10 mg/day) for 90 days. The effectiveness of the two treatments was assessed on clinical grounds and by evaluating at monthly intervals serum progesterone levels, during the presumed luteal phase, and serum prolactin levels. The success rate with the two drugs was superimposable in terms of disappearance of galactorrhea and return of menses, normalization of prolactin levels and induction of ovulation. Also the number of pregnancies obtained (7 with metergoline, 9 with bromocriptine) was similar. With both drugs, the majority of patients responded to the treatment within the first month.

Adenoma↗

Ovulation induction in the estrogenized anovulatory patient.

Ovulation induction is one of the greatest success stories in reproductive endocrinology. With appropriate therapy in properly f1p4cted patients, the conception and live birth-rates in treated patients are almost indistinguishable from normal. In the estrogenized woman there are many different techniques to reverse the condition of chronic anovulation. With clomiphene citrate, up to 80% of patients will ovulate, and approximately half will conceive. In women who fail clomiphene therapy, injectable gonadotropins are usually successful in inducing ovulation. New protocols for administering these powerful agents have minimized the risk of ovarian hyperstimulation and multiple pregnancy. When medical therapy fails to result in successful ovulatory cycles, surgical treatments can be considered. Laparoscopic ovarian ablation has been shown to be effective treatment. Whether this less invasive surgery results in fewer adhesions than conventional ovarian wedge resection remains to be proven. By carefully considering each patient and individualizing treatment based on a full knowledge of alternatives, ovulation induction remains one of the most challenging and rewarding treatments in reproductive endocrinology.

Anovulation↗

Does ovarian blood flow distinguish between ovulatory and anovulatory patients with polycystic ovary syndrome?

OBJECTIVE: The purpose of this study was to determine whether parameters of ovarian blood flow distinguish between women with polycystic ovary syndrome (PCOS) who ovulate and those who are anovulatory. STUDY DESIGN: This was a prospectively enrolled trial, carried out as a cross-sectional comparison of 12 ovulatory patients with PCOS and 20 matched subjects with classic PCOS and 10 healthy control subjects. Hormonal parameters and ovarian blood flow by color flow Doppler imaging were obtained in the early follicular phase. RESULTS: Characteristic elevations in luteinizing hormone (LH) and androgens were found in both groups with PCOS compared with control groups. Women with anovulatory PCOS had high insulin levels and lower Quantitative Insulin-Sensitivity Check Index (QUICKI) values compared with women with ovulatory PCOS, although both groups had values that were different from healthy control subjects (P<.01). Ovarian volume was similar in the two groups with PCOS, but pulsatility and resistance indices were lower in anovulatory PCOS (P<.01) compared with ovulatory PCOS and control subjects, who had similar findings. Insulin correlated negatively with the resistance index and QUICKI correlated positively (r=0.653, P<.01). There was a negative correlation between the resistance index and unbound testosterone (r=-0.5, P<.05). CONCLUSION: These data suggest that differences in ovarian blood flow in anovulatory versus ovulatory women with PCOS and that hormonal factors, including insulin resistance, may influence this relationship. The alterations in blood flow in anovulatory PCOS may contribute toward or result from anovulation.

Adult↗

Dysfunctional uterine bleeding. Clarifying its definition, mechanisms, and management.

"Dysfunctional uterine bleeding" is not a generic term for abnormal uterine bleeding. Rather, it refers solely to bleeding caused by an ovarian endocrinopathy. Estrogen withdrawal and inappropriately sustained estrogen production are the two mechanisms responsible. The latter mechanism produces estrogen breakthrough bleeding, which is common in women with chronic anovulation. Treatment of estrogen withdrawal bleeding depends on when in the menstrual cycle bleeding occurs. Anovulatory bleeding is best treated with progestin. Estrogen therapy is contraindicated, except in patients with profuse anovulatory bleeding unresponsive to progestin treatment, because it increases the risk of endometrial hyperplasia and cancer.

Adenocarcinoma↗

The anovulatory patient. An orderly approach to evaluation and treatment.

Ovulatory dysfunction is a leading cause of female infertility in the United States. Fortunately, ovulatory dysfunction is often amenable to treatment. Thorough testing is necessary to identify the exact cause of anovulation before conventional ovulation-inducing therapy is started. Careful patient monitoring is essential to avoid risks such as the ovarian hyperstimulation syndrome. Several newer ovulation-inducing agents are available for use in special situations.

Anovulation↗

Diagnosing infertility in a district general hospital: a case-note and cost analysis.

This study aimed to observe diagnostic work-up and cost evaluation of infertile couples to identify opportunities for improvement. One hundred and seventy-four new referrals to the gynaecology clinic in a District General Hospital during 1996 and 1997 provided the cohort for analysis. Data from case notes were transferred on to data collection sheets. Data were inputted into SPSS for analysis. Primary infertility accounted for 62% of couples. One hundred and forty-two couples (81.6%) had a definitive diagnosis, and the analyses relate to these couples only. There was no single investigation performed on the whole cohort studied. Semen analysis was undertaken in 80.3% of the couples; couples with suspected male infertility were over four times more likely to have had more than two semen tests (P = 0.0005); 77.5% of couples had FSH and LH tests; and midluteal progesterone was tested in 76.1%. An increased intensity of FSH-LH hormone testing was associated with couples with anovulation (chi(2) = 6.79, P = 0.03). Serial repeat progesterone tended to be given to women with irregular or prolonged cycles (35 days or more), although this tendency was not statistically significant. The most common test for tubal patency was hysterosalpingography. Higher costs are generally associated with diagnosing endometriosis and tubal factor because of the relatively high cost of laparoscopy. The average cost of diagnosis for each patient was pound 365 and ranged from pound 64 to pound 851. In conclusion, a standard protocol of basic investigative procedures should be offered in secondary centres to all couples. Avoiding duplication and unnecessary investigations (for example, serial progesterone) may reduce costs, although offering all couples a standard protocol of tests would probably offset this observation.

Anovulation↗

Seasonal adiposity and delayed ovulation in a vespertilionid bat, Scotophilus heathi: role of tumor necrosis factor-alpha.

The aim of this article was to evaluate the physiological significance of tumor necrosis factor-alpha (TNF-alpha) in seasonal accumulation of adipose tissue, hyperinsulinemia, and anovulation in Scotophilus heathi. The result showed seasonal variations in the circulating TNF-alpha level. A higher level of circulating TNF-alpha was observed during quiescence and recrudescence, whereas a lower level of TNF-alpha was observed during winter dormancy and the preovulatory period. An increased circulating TNF-alpha level coincided closely with accumulation of adipose tissue and hyperinsulinemia. Immunocytochemical localization of TNF-alpha in the ovary showed immunoreactivity mainly in the oocytes and theca-interstitial cells. The oocytes of small and medium-sized follicles showed strong TNF-alpha immunostaining, whereas weak immunoreactivity was observed in the large antral follicles. The atretic follicles showed mild TNF-alpha immunostaining. TNF-alpha immunoreactivity in the ovary was slightly higher during the quiescence and preovulatory periods compared with the periods of recrudescence and winter dormancy. TNF-alpha alone significantly increased androstenedione and estradiol production by the ovary in vitro but did not augment the luteinizing hormone (LH)-induced androstenedione production. However, TNF-alpha did augment LH-induced estradiol production. The results of this study suggest the involvement of TNF-alpha in the interaction among adipose tissue accumulation, insulin resistance, and ovarian activity in S. heathi.

Adipose Tissue↗

Circulating immunoreactive and bioactive follicle stimulating hormone concentrations in anovulatory infertile women and during gonadotrophin induction of ovulation using a decremental dose regimen.

Our purpose was to determine whether decreased follicle stimulating hormone (FSH) activity, either systemic or at the follicular level, is involved in impaired follicle growth associated with normogonadotrophic anovulation. To differentiate between the possible levels of disturbance, bioactive (BIO-FSH; using the in-vitro rat granulosa cell aromatase bioassay) and immunoreactive (IRMA-FSH) FSH serum concentrations of three groups of subjects were compared: (i) 172 normogonadotrophic anovulatory infertile women during baseline conditions, (ii) 22 clomiphene-resistant polycystic ovary syndrome patients undergoing ovulation induction by exogenous gonadotrophins using a decremental dose regimen, and (iii) nine regularly cycling controls. BIO-FSH [13.2 (range 0.8-29.5) IU/l] and IRMA-FSH [4.4 (range 1.2-9.3) IU/l] concentrations in anovulatory women during baseline conditions were significantly lower than maximum concentrations reached during the follicular phase in controls [18.7 (13.2-23.4) and 6.4 (5.7-10.0) IU/l respectively], but were not significantly different from initial concentrations in controls [10.4 (7.2-19.6) and 4.8 (2.8-8.2) IU/l respectively]. Moreover, concentrations of IRMA-FSH and BIO-FSH were negatively correlated (r = -0.25, P = 0.01, and r = -0.24, P = 0.02 respectively) with the interval between last vaginal bleeding and blood sampling. Maximum concentrations of IRMA-FSH [7.6 (3.9-10.9) IU/l] during ovulation induction by gonadotrophins were not significantly different from maximum [6.4 (5.7-10.0) IU/l] concentrations in controls, whereas maximum BIO-FSH concentrations [13.5 (8.7-17.4) versus 18.7 (13.2-23.4) IU/l] were significantly lower. Our findings suggest that (i) circulating FSH does not reach concentrations that are sufficient to induce normal follicle development in anovulatory women during baseline conditions, and (ii) the FSH threshold for ovarian stimulation of this patient group is not different from normal.

Adult↗

A comparative prospective study of a chronic low dose versus a conventional ovulation stimulation regimen using recombinant human follicle stimulating hormone in anovulatory infertile women.

The efficacy and safety of a chronic low dose (group A) and a conventional (group B) stimulation regimen of recombinant human follicle stimulating hormone (r-HFSH) were compared in 103 WHO Group II infertile women with clomiphene citrate-resistant anovulation. Mono- or bifollicular development was induced in 88.1% of patients in group A compared with 76.1% in group B. Ovulation and pregnancy rates were higher in group A (71.4% and 33.3%, respectively) than in group B (63.0% and 20%), but these differences were not statistically significant. Additionally, the total number of follicles that were >10 mm diameter was lower in group A than group B (3.0+/-2.6 versus 6.3+/-6.5; P < 0.0001), as was the oestradiol concentration (504+/-477 pg/ml versus 988+/-740 pg/ml; P < 0.03). The median dose of FSH (75 IU ampoules) used per cycle was 11 ampoules in group A and 12.5 in group B. In terms of the incidence of ovarian hyperstimulation syndrome, no differences were recorded between the two groups. The results demonstrated that r-HFSH is effective and safe in both these treatment protocols. The chronic low dose regimen was associated with a trend towards a higher rate of mono- or bifollicular development, without jeopardizing the incidence of pregnancy.

Adult↗

Ovulation induction with low dose alternate day recombinant follicle stimulating hormone (Puregon).

We investigated whether a recombinant follicle stimulating hormone (FSH) (Puregon) can be administered less frequently and at lower doses during ovulation induction than is current practice. Patients (20-35 years, body mass index <30 kg/m(2)) with infertility and chronic anovulation secondary to polycystic ovarian syndrome and resistant to previous clomiphene treatment received (Puregon); 100 IU, n = 17 patients, or 50 IU, n = 10 patients) on alternate days. After 2 weeks and in the absence of follicular recruitment, doses were increased stepwise at weekly intervals (50 IU/alternate days). Twenty-two cycles out of 27 were ovulatory. There were six pregnancies, five from Puregon (100 IU) and one from Puregon (50 IU); four pregnancies proceeded to term. The duration of stimulation (mean, range) with Puregon (100 IU) was 16.4, 7-29 and Puregon (50 IU) 19.1, 8-38 days. The gonadotrophin doses administered (mean; range) were 689, 200-1800 IU (Puregon 50 IU) and 939, 400-2300 IU (Puregon 100 IU). We conclude that low dose alternate day Puregon treatment is suitable for this difficult patient group.

Adult↗

The role of changing pulse frequency in the regulation of ovulation.

Ovulatory cycles in women result from sequential stimulation of ovarian follicular development by pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH). In the follicular phase the initial FSH stimulus declines and LH secretion increases toward the mid-cycle ovulatory surge. During the luteal phase gonadotrophin secretion is reduced. This reflects the effects of ovarian steroids inhibiting the frequency of gonadotrophin releasing hormone (GnRH) secretion by the hypothalamus, and the direct effects of oestradiol and inhibin to reduce gonadotroph (FSH) secretion. The frequency of GnRH stimulation of the gonadotroph is a selective regulator of gonadotrophin synthesis, with slow frequency stimuli favouring FSH and faster frequency stimuli favouring LH secretion. Current research has only revealed a single gonadotrophin releasing hormone. Thus, the ability to change the pattern (particularly frequency) of GnRH stimulation of the gonadotroph is proposed as an important regulator of differential FSH and LH synthesis, and hence of ovulatory cycles. In some disorders of ovulation the ability to regulate GnRH pulse frequency appears to have been lost. Slow frequency GnRH pulses are consistently seen in women with hypothalamic amenorrhoea and hyperprolactinaemia. The reduced GnRH secretion appears to reflect increased hypothalamic opiate tone and can be rapidly reversed with an opiate receptor blocker. Other disorders associated with anovulation show rapid frequency GnRH secretion, and polycystic ovarian syndrome (PCO) is commonly associated with fast-frequency, high-amplitude LH (GnRH) pulses. Such a GnRH stimulus would favour LH and androgen production and the failure of ovarian follicular maturation in PCO may reflect inappropriate sequential FSH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anovulation↗

Role of gonadotrophin releasing hormone secretory dynamics in the control of the human menstrual cycle.

The pattern of episodic gonadotrophin releasing hormone (GnRH)-driven luteinizing hormone (LH) secretion changes dynamically across the human menstrual cycle. Adherence to a specific regimen of pulse amplitude and frequency is critical for normal ovulation, menstrual cyclicity and reproductive function. Derangements of episodic LH secretion are associated with anovulation. We have shown that in the human slowing of GnRH-induced LH pulses results in lower ovulatory rates and dysfunctions of the mid-cycle LH surge. This information is relevant for the understanding of the endocrine dynamics of the menstrual cycle both in normal and anovulatory subjects.

Anovulation↗