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PubMed1976

Human pituitary gonadotrophin index. II LHRH test and clomiphene response before and after LHRH stimulation.

To monitor the effect of LHRH treatment on hypothalamo-pituitary-gonadal function, women with functional amenorrhoea were investigated by standardized LHRH and repeated clomiphene tests before and after LHRH therapy. The actual pituitary gonadotrophin reserve was defined by a Human Pituitary Gonadotrophin Index (HPGI). Clomiphene response served as hypothalamic function test, plasma oestradiol and progesterone concentrations were measured for assessment of the gonadal function. LHRH treatment as performed in this study did not change basal gonadotrophin levels or the pituitary responsiveness in our standardized LHRH test. Plasma oestradiol concentrations remained unaltered at the lower limit of the early follicular phase values of a normal menstrual cycle. The inability to respond to clomiphene was changed to clomiphene responsiveness during therapy in eighteen out of twenty-nine women with anovulation. The majority of the responders had HPG-Indices of R2. Patients with hyperprolactinaemic anovulation did not convert. The possibility of an ultrashort feedback action of LHRH on its own production in the human is discussed.

Adult↗
PubMed1994

Obstetric and gynecologic dysfunction in the Ehlers-Danlos syndrome.

Women members of the newly formed Ehlers-Danlos National Foundation (EDNF) were surveyed with a very detailed questionnaire with 50 questions concerning family history and inheritance, past medical history, and obstetric and gynecologic problems. They entailed the largest extant database on Ehlers-Danlos Syndrome (EDS) patients. The mean age of the 68 women who responded to the survey was 42 years; most had EDS types I, III, IV and unknown. Forty-three women had 138 pregnancies; 13 women never married. The stillbirth rate was 3.15% (3/95); the preterm delivery rate was 23.1% (22/95), and the spontaneous abortion rate was 28.9% (40/138). There was a cesarean delivery rate of 8.4%, with 14.7% having perinatal bleeding problems. One woman (EDS type IV) had congestive heart failure. Common gynecologic problems were recurrent anovulation (41.3%), recurrent vaginal infections (53%), abnormal cytologic smears (19%), sexual dysfunction (61%), irregular menses (28%), endometriosis (15.8%), vaginal dryness (25%) and a need for hysterectomy (19.1%). In this largest series of pregnancies with EDS, we found relatively high rates of abortion, preterm delivery, pregnancy-related bleeding and stillbirth. Women with EDS also seem to have high frequency of anovulation, vaginal infections, abnormal cytologic smears and dyspareunia.

Abortion, Spontaneous↗
PubMed1993

Clinical manifestations and treatment of dysfunctional uterine bleeding.

Dysfunctional uterine bleeding is a common gynecologic disorder that can affect any woman during her reproductive years. It is a diagnosis of exclusion, and the clinician must proceed through a logical stepwise evaluation to rule out all other causes of the abnormal bleeding. In most cases dysfunctional uterine bleeding is associated with anovulation. During the pubertal and perimenopausal periods, anovulatory bleeding is a common occurrence. During these transitional states, the abnormal bleeding has a physiological basis and is secondary to an estrogen withdrawal. Anovulatory bleeding can also be associated with chronic anovulation. The chronic unopposed estrogen that characterizes this disorder causes a continuous proliferation of the endometrium; this can result in abnormal bleeding and place the patient at risk for endometrial cancer. The goals of treatment for anovulatory bleeding are to stop the acute bleeding, avert future episodes, and prevent long-term complications. In some cases surgical intervention is indicated, but the foundation of treatment has been a medical approach. Several progestational agents have demonstrated effectiveness and can be administered either orally or by intramuscular injection. If the patient fails to have resolution of the bleeding with medical therapy, another cause of the bleeding must be suspected, and reevaluation is necessary.

Anovulation↗
PubMed1993

[Treatment of secondary adolescent amenorrhea with purified FSH].

The dysfunctional features of adolescent secondary amenorrhea are here considered: anovulation, immaturity of estrogenic feed back, multi-follicular ovary. We described the opportunity of using gonadotrophin in the treatment of hypogonadotrophic amenorrhea. Among 64 patients with menstrual delay, we examined a group of 23 selected girls, 21 of them affected by secondary amenorrhea and 2 affected by primary amenorrhea; their average age is 17 years. The selection excludes organic and psychiatric pathologies, while includes anovulation, low rates of FSH and inadequate response to LHRH test, multi-follicular ovary. Some patients were also affected by acne, hypertrichosis, weight disorders, emotional stress. The therapeutic approach with purified FSH (urofollitrophin) is described on an amount of 48 treatments. We used 75/225 UI/day at 3 degrees to 5 degrees/7 degrees of each menstrual cycle, and for 3/5 cycles. Doses are in some subjects modified during the treatment in relation to menstrual response. Hormonal, echographic and clinical evaluation were given before and after each treatment. The results of giving FSH demonstrate an 81.2% of immediate success, while an 43.7% up to 12 months. We observed a significant reduction of LH rates as well as estrogenic increase and subsequent menstrual response. Ovarian follicles increased in number and volume, while no hyperstimulation effects appeared. In general we suppose these data are satisfactory; nevertheless we point out the opportunity of only treat selected patients, even in considering the complaint due to this therapeutic engagement and the eventual consequent renouncing.

Adolescent↗
PubMed1995

Induction of multifollicular growth in patients non responding to clomiphene citrate and gonadotropins or gonadotropins only.

OBJECTIVE: We aimed at inducing multifollicular recruitment in patients with chronic anovulation-resistant to Clomiphene Citrate (CC) and/or exogenous gonadotropins. DESIGN: At the II Department of Obstetrics and Gynecology we treated our patients with exogenous gonadotropins and concomitant endogenous gonadotropin suppression obtained by the use of a GnRH analog (Buserelin). PATIENTS: We studied 14 patients with chronic anovulation due to either hypothalamic dysfunction or polycystic ovarian syndrome. MEASUREMENTS: We monitored the follicular growth ultrasonographically from the eighth day of the menstrual cycle, and assessed E2 and LH daily dosage from the tenth day. RESULTS: With this protocol we obtained 2 or 3 mature follicles, and reached an ovulatory rate of 80.7% and a pregnancy rate of 71.4%. Premature luteinization never occurred, and progesterone increase took place only after human chorionic gonadotropins administration.

Adult↗
PubMed1979

Evaluation of the carcinogenic effects of estrogens, progestins and oral contraceptives on cervix, uterus and ovary of animals and man.

Estrogens do not have the general biological effect of increasing the occurrence of cancer in various species of laboratory animals. The neoplastic effect of estrogens in animals is strain and species dependent. Estrogens may increase the incidence of uterine cervical cancer in some strains of mice, but not in other strains or other animal species. The progestins and oral contraceptives (OC) have not induced cervical cancer in animals and most studies demonstrate that the steroid anovulants do not increase the occurrence of abnormal cervical smears or cervical cancer in women. Estrogens increase the occurrence of endometrial cancer in the rabbit, occasionally in the mouse, but apparently not in other species. Case-control studies in menopausal and postmenopausal women indicate an increased risk of endometrial carcinoma (EC) associated with use of estrogen. However, in other studies estrogen has not been related to EC. Cases of EC have been reported in women using sequential OC but a causal relationship has not been established. Progestins alone may arrest progress or cause regression of EC in women. EC has not been related to use of the combination OC, and it is unlikely that use of these anovulants will lead to the development of endometrial cancer. Estrogens or OC do not induce a carcinogenic response in the ovary. A decrease in ovarian cysts, is observed during the clinical use of OC.

Animals↗
PubMed1985

The Estes operation (transposition of one ovary to the uterine cavity): its results in the rabbit model.

Pregnancies have been reported after the Estes procedure (EP). These results have not been duplicated in modern attempts. The recent report of intrauterine fertilization in humans gives support to the feasibility of this procedure as a possible alternative to in vitro fertilization. An animal model is needed to evaluate the outcome of this operation. Consequently, 14 mature New Zealand white rabbits had one ovary placed in the uterine cavity after contralateral oophorectomy and bilateral salpingectomy. One month later, the animals were mated with a fertile buck. Fourteen to 16 days after that, the outcome was evaluated. Twenty-five to 75% of the ovarian surface was exposed to the uterine lumen, and no evidence of ovulation or implantation was found. The lack of pregnancies was attributed to an ovulatory dysfunction. Anovulation after the EP may also occur in the clinical situation, as suggested by one histologic study. The ovulatory function of these patients has not been characterized in the literature. Documentation of a successful intrauterine fertilization with delivery of a term baby supports the theoretical feasibility of the EP; however, anovulation incurred by our procedure appears to be the major drawback.

Animals↗
PubMedDate not supplied

Role of GnRH drive in the pathophysiology of polycystic ovary syndrome.

Polycystic ovary syndrome may result from multiple mechanisms, but full expression of the PCO syndrome with hyperandrogenic anovulation depends upon sustained LH drive and relative FSH deficiency. We have described possible intrinsic and extrinsic factors capable of modifying the hypothalamic-pituitary-ovarian axis. Available evidence suggests the presence of an intrinsic alteration in GnRH-LH drive. The long-term natural history of HAA is variable and depends on several factors including obesity, aberrations in insulin action, intrinsic ovarian function, and end-organ responsiveness to androgens. Figure 1 presents a conceptualization of the pathogenesis of PCOS diagramming the multiple modulators of its expression. Long-term suppression of androgens when fertility is not desired should modify the full expression of the PCO syndrome. It is important to appreciate that therapy with oral contraceptive agents has few drawbacks and many immediate and potential long-term benefits for women with HAA. This therapy may be of greatest benefit when started in adolescence prior to the progression of obesity, hirsutism, and thecal-stromal hyperplasia. Women with HAA represent a large subgroup of patients who require individualization of their health care with sensitivity to issues surrounding anovulation, obesity, hirsutism, and infertility.

Female↗
PubMed1994

Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances.

OBJECTIVE: Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances. The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern, using treatment with cyclic medroxyprogesterone, with or without calcium supplementation, in physically active women with disturbed menstruation. DESIGN: This study was a 1-year randomized, double-blind, placebo-controlled trial. Women who were stratified by menstrual cycle disturbance were randomized into four groups. The outcome variable was the change in spinal bone density measured by dual energy techniques. SETTING: A large metropolitan area. PARTICIPANTS: Sixty-one healthy, normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea, oligomenorrhea, anovulation, or short luteal phase cycles completed the study. INTERVENTION: Therapies were cyclic medroxyprogesterone (10 mg/day for 10 days per month) and calcium carbonate (1,000 mg/day of calcium) in four groups: (A) (n = 16) cyclic medroxyprogesterone plus calcium carbonate; (B) (n = 16) cyclic medroxyprogesterone with calcium placebo; (C) (n = 15) placebo medroxyprogesterone with active calcium; or (D) (n = 14) both medroxyprogesterone and calcium placebos. RESULTS: The initial bone density (mean = 1.12 g/cm2) did not differ by group (P = 0.85). The 1-year bone density change was strongly related to treatment with medroxyprogesterone (P = 0.0001) and weakly to calcium (P = 0.072) treatment. Bone density increased significantly (+1.7% +/- 0.5%, +/- SEM, P = 0.004) in the medroxyprogesterone-treated groups (A and B), did not change in the calcium-treated group (C) (-0.7% +/- 0.6%, P = 0.28), and decreased on both placebos (D) (-2.0% +/- 0.6%, P = 0.005). CONCLUSIONS: Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances. POTENTIAL CLINICAL SIGNIFICANCE: Amenorrhea, oligomenorrhea, anovulation, and short luteal phase cycles are common in premenopausal women and associated with spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing. This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group, whereas those subjects in the placebo group lost bone. Calcium supplementation appeared to be helpful but did not reach statistical significance. The implications of these findings for the prevention of osteoporosis warrant further investigation.

Adult↗
PubMed1977

Effect of synthetic thyrotropin-releasing hormone on ovulation in baboons.

Twice daily oral thyrotropin-releasing hormone administered to female baboons throughout the menstrual cycle had no significant influence on cycle length or upon estrogen levels but produced blunted midcycle LH peaks and luteal phase progesterone levels in three fourths of the treatment cycles. Mean plasma prolactin levels were increased approximately 2.5-fold relative to untreated, ovulatory control cycles. CB-154 alone did not alter cycle length or endocrine parameters examined (mean prolactin levels were decreased but not significantly). Cycles during which CB-154 was administered concomitantly with TRH were characterized by normal ovulation as evidenced by luteal phase progesterone levels. Since the effect on LH secretion was reversed by concomitant CB-154 administration, TRH-induced anovulation in animals given long-term treatment appeared to be mediated through physiologic mechanisms sensitive to elevated circulating prolactin levels. However, this conclusion must be considered equivocal since prolactin levels were also elevated during ovulatory cycles following long-term TRH therapy. Finally, these data do no exclude the alternative possibility that anovulation in baboons given long-term TRH treatment was a reflection of thyroid disturbance and not directly attributable to elevated prolactin.

Animals↗
PubMed1989

Pathophysiology of polycystic ovary syndrome.

The pathophysiology of polycystic ovarian syndrome (PCO) is the subject of many hypotheses and speculations. In particular, the possible intervention in the starting and the maintenance of this syndrome of hyperprolactinemia, androgen hypersecretion, decreased FSH secretion is discussed. A primary abnormality at the level of the GnRH generator responsible for an increase of GnRH pulses frequency and amplitude remains an attractive hypothesis, at least in pure PCO syndrome. However, the possibility that other factors may contribute to the maintenance of a vicious circle of anovulation cannot be neglected. Regarding the treatment of chronic anovulation and hirsutism currently observed in PCO syndrome, only agents acting at the hypothalamic level are efficient, namely: clomiphene citrate for inducing ovulation and antigonadotropic therapies for improvement of hirsutism. These different possibilities are discussed.

Androgens↗
PubMed2004

The role of ovarian surgery in polycystic ovary syndrome.

Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation are well recognized. In 1935, Stein and Leventhal first described surgical treatment by ovarian wedge resection at laparotomy for women with anovulation and PCOS. Ovarian wedge resection was eventually abandoned because of the significant risk of postsurgical adhesion formation, which resulted in tubal adhesions, and because of the advent of medical ovulation induction with clomiphene and gonadotrophins. However, since the arrival of minimally invasive surgical techniques, laparoscopic ovarian surgery has become feasible. The potential advantages of laparoscopic ovarian surgery include repeated single ovulations and less adhesion formation. Lowered costs make ovarian surgery an attractive alternative to gonadotrophins. However, although many case series have suggested that ovarian surgery is an effective strategy, few randomized, controlled trials have been undertaken comparing the success rates of surgery with gonadotrophins. The long-term concerns with surgery include adhesion formation and premature ovarian failure.

Cost-Benefit Analysis↗
PubMed2005

Persistent estrus rat models of polycystic ovary disease: an update.

OBJECTIVE: To critically review published articles on polycystic ovary (PCO) disease in rat models, with a focus on delineating its pathophysiology. DESIGN: Review of the English-language literature published from 1966 to March 2005 was performed through PubMed search. Keywords or phrases used were persistent estrus, chronic anovulation, polycystic ovary, polycystic ovary disease, and polycystic ovary syndrome. Articles were also located via bibliographies of published literature. SETTING: University Health Sciences Center. INTERVENTION(S): Articles on persistent estrus and PCO in rats were selected and reviewed regarding the methods for induction of PCO disease. MAIN OUTCOME MEASURE(S): Changes in the reproductive cycle, ovarian morphology, hormonal parameters, and factors associated with the development of PCO disease in rat models were analyzed. RESULT(S): Principal methods for inducing PCO in the rat include exposure to constant light, anterior hypothalamic and amygdaloidal lesions, and the use of androgens, estrogens, antiprogestin, and mifepristone. CONCLUSION(S): The validated rat PCO models provide useful information on morphologic and hormonal disturbances in the pathogenesis of chronic anovulation in this condition. These studies have aimed to replicate the morphologic and hormonal characteristics observed in the human PCO syndrome. The implications of these studies to human condition are discussed.

Animals↗
PubMed1998

Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.

Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance.

Androgens↗
PubMed2001

Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.

OBJECTIVE: To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.

Adolescent↗
PubMed1992

Cost-effectiveness of gamete intrafallopian transfer in comparison with induction of ovulation with gonadotropins in the treatment of female infertility: a clinical trial.

OBJECTIVE: To compare the cost-effectiveness of gamete intrafallopian transfer (GIFT) with that of conventional infertility treatment in couples with female infertility, excluding tubal factors. DESIGN: Patients were randomly divided in two groups: receiving GIFT or conventional infertility treatment. For a period of 2 years, GIFT was compared with conventional infertility treatment in couples with endometriosis, anovulation, idiopathic infertility, cervical mucus factor, female immunologic factor, or multifactorial causes of infertility in a randomized clinical trial. SETTING: The study was performed in the Unit for Human Reproduction, Department of Obstetrics and Gynaecology, Faculty of Medicine, University of the Orange Free State, Bloemfontein, Republic of South Africa. PATIENTS: One hundred seventy-four successive couples with female infertility were selected for the study. All couples were from the higher socioeconomic bracket. INTERVENTIONS: One group received GIFT and the other received conventional infertility treatment consisting of induction of ovulation with gonadotropins followed by intrauterine artificial insemination or normal intercourse. MAIN OUTCOME MEASURES: The results were stratified according to the specific cause of infertility. Outcome was measured by the success rate per treatment cycle, as well as the cost per pregnancy. RESULTS: Overall, GIFT proved to be successful in 26.7% of treatment cycles compared with 9.7% with conventional therapy. CONCLUSIONS: After careful analysis, the authors came to the conclusion that GIFT is more cost-effective than conventional infertility treatment in patients with endometriosis and anovulation. In patients with idiopathic infertility, immunologic infertility, a cervical mucus factor, and multifactorial infertility, induction of ovulation followed by intrauterine artificial insemination or normal intercourse proved to be more cost-effective.

Coitus↗
PubMed1993

The value of luteal support with progesterone in gonadotropin-induced cycles.

OBJECTIVE: To evaluate the effect of luteal support with vaginal P suppositories in hMG- and hCG-induced cycles. DESIGN: Between March 1988 and February 1989 patients did not receive luteal support, while between March 1989 and January 1990 P was given routinely in the luteal phase. Induction protocol and patient selection remained otherwise unchanged. SETTING: Infertility clinic of a tertiary care hospital. PATIENTS: Twenty-seven patients with hypogonadotropic amenorrhea (World Health Organization [WHO] group I) (11 women with luteal support, 16 women without) and 102 patients with euprolactinemic clomiphene citrate (CC)-resistant anovulation (WHO group II) (52 women with luteal support, 50 women without). INTERVENTION: Vaginal P suppositories 200 mg/d in the luteal support group. MAIN OUTCOME MEASURES: Pregnancy rate (PR), pregnancy outcome. RESULTS: The overall PR in 118 cycles with luteal support was 26.3% whereas 10.4% pregnancies were achieved in 115 cycles of the control group. The influence of luteal support was more pronounced in patients with CC-resistant anovulation (25.2% versus 6.9%) than in patients with hypogonadotropic amenorrhea (33.3% versus 21.4%, not significant). The abortion rate was not significantly changed. CONCLUSION: Luteal support with P increases the PR after hMG and hCG induction. The need for supplementary P seems to be related to the underlying cause of ovarian disturbance.

Abortion, Spontaneous↗
PubMed1996

Serum from women with polycystic ovary syndrome inhibits fertilization and embryonic development in the murine in vitro fertilization model.

OBJECTIVE: To study the effects of serum collected from women with polycystic ovary syndrome (PCOS) on the fertilization and early embryonic development of the murine oocyte. DESIGN: Sera from women with anovulation were used as a supplement in a murine IVF model. SETTING: Tertiary care academic medical center. PATIENTS: Four fertile, four hypothalamic amenorrheic, seven PCOS (three with elevated LH and four with elevated T), and three anovulatory women with normal hormone levels. RESULTS: When compared with serum from fertile women, serum from women with PCOS reduced fertilization rates (60% versus 42%) and subsequent early embryonic development rates (87% versus 31%). Serum from women with PCOS and elevated T levels had the lowest fertilization rates (22%). Polycystic ovary syndrome serum with elevated T or LH levels significantly decreased early embryonic development rates in comparison to fertile women (22%, 41% versus 87%). CONCLUSIONS: Serum from women with PCOS inhibited fertilization and blastocyst development. Because both T and LH caused inhibited blastocyst development, these data have implications regarding low pregnancy rates and live birth rates during ovulation induction in women with anovulation. These data also raise questions regarding the use of serum during IVF.

Amenorrhea↗