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PubMed1976

Hypothalamic gonadotropin releasing hormone: physiologic and clinical considerations.

Despite the efforts of a large number of investigators, the role of GnRH in clinical gynecology is uncertain. At present, its greatest utility is in research directed toward the understanding of hypothalamic-pituitary interrelationships. However, a clear understanding of the hypothalamic control of gonadotropin secretion awaits the actual measurement of the secretion of GnRH by the hypothalamus. In addition, a better understanding of the ability of the pituitary to secrete gonadotropins in various disorders of menstruation and maturation will probably be achieved through the determination of the capacity of the pituitary to synthesize as well as release gonadotropins in response to GnRH. Such determinations will probably utilize repeated or continuous infusions of GnRH rather than the currently more popular single injection technique. Finally, GnRH may be useful in the induction of ovulation. A definition of its role in ovulation induction awaits the results of additional clinical studies. Understanding of the nature of hypothalamic control of the pituitary is as yet incomplete. The availability of hypothalamic releasing factors will make it possible to study in greater detail the mechanisms by which the fine regulation of the endocrine system is achieved.

Adenoma↗
PubMed1998

Adverse effects of luteinizing hormone on fertility: fact or fantasy.

High tonic serum concentrations of luteinizing hormone (LH) in the follicular phase, frequently witnessed in polycystic ovary syndrome, have been associated with decreased reproductive function. Impaired rates of fertilization, conception and miscarriage are obtained when LH levels are high before oocytes are collected, during ovulation induction or in women with regular cycles. Conversely, treatment that decreases LH concentrations, such as gonadotrophin-releasing hormone analogue or laparoscopic ovarian puncture, eases induction of ovulation and pregnancy and improves miscarriage rates. Tonic hypersecretion of LH appears to induce premature oocyte maturation, causing the problems with fertilization and miscarriage.

Abortion, Spontaneous↗
PubMed1989

[The value of hormonal and sonographic parameters in the diagnosis of disordered and normal early pregnancy].

In 112 clinical pregnancies after IVF/ET or GIFT, the importance of beta-HCG progesterone and 17 beta-estradiol was evaluated. Additionally, we performed a vaginosonography to confirm an early intrauterine pregnancy. The aim of the study was to define, when a clinical pregnancy can be detected as early as possible and when the differential diagnosis of intact or abnormal pregnancy can be made. By measuring E2 in an HCG substituted cycle, the diagnosis of a clinical pregnancy is possible as soon as day +12 after induction of ovulation. When considering beta-HCG levels alone, the same diagnosis can be made at day +18. Single determinations of HCG level do not offer a satisfactory diagnosis, because of intra-individual variations. A progesterone drop always demonstrates a disturbed early pregnancy. Using a combination of hormonal serial measurements of HCG, E2, progesterone and vaginosonography, the diagnosis of an intact intrauterine pregnancy should be possible as early as day +27 after ovulation induction.

Abortion, Spontaneous↗
PubMed1999

Comparison of ovarian electrocautery and oral contraceptives in the treatment of hyperandrogenism in women with polycystic ovary syndrome.

BACKGROUND: Endocrine treatment of hyperandrogenism in women with polycystic ovary syndrome (PCOS) aims at reduction of androgens and increasing sex hormone binding globuline (SHBG), which are also side effects of ovarian electrocautery (OE) when used for induction of ovulation. METHODS: Hormonal effects of ovarian electrocautery were compared with the effects of oral contraceptives (OC) containing desogestrel (DG) or cyproteron acetate (CPA). OCs were given to 18 women with PCOS as their sole treatment (group A) and to 23 women after the restoration of regular ovulatory cycling by ovarian electrocautery (group B). RESULTS: Ovarian electrocautery induced ovulation and increased the concentration of estrogens and especially progesterone, while OC induced the opposite effects. In the androgens and SHBG the two treatments induced changes that were in the same direction, but OC treatment induced changes that exceeded those of OE. The concentration of SHBG increased from 27.9 to 127.7 nmol/L on OC treatment (Group A), compared with 37.2 to 44.9 after OE (Group B). The androgens decreased, for testosterone the decreases were 2.1 and 0.99 nmol/L, respectively, for androsterone 5.36 and 3 nmol/L, for dihydrotestosterone 0.12 and 0.1 nmol/L, and for DHEAS 3.28 and 1.8 umol/L. No further gain was obtained by the combination of the two treatments. CONCLUSIONS: Hyperandrogenism in women with PCOS can be effectively treated with OCs containing DG or CPA. In women with concurrent infertility, however, ovarian electrocautery can be recommended. The only indication for the combination of these two treatments is ambivalence with regard to the fertility after ovulation induction by OE. A temporary delay of ovulatory cycling with OC-treatment after OE has no negative impact upon the future fertility.

Adult↗
PubMed1991

Combination of long and short term GnRH analogue protocols: a new therapeutic approach to persistent high progesterone levels in IVF cycles.

Thirty-four patients who had had persistently high progesterone (P) levels during menotrophin therapy in previous in-vitro fertilization (IVF) cycles, despite pretreatment with a long acting gonadotrophin-releasing hormone analogue (GnRHa), were randomly divided into two groups according to the mode of ovulation induction used. In 16 women (group 1), induction of ovulation was performed with decapeptyl (DTRP6)/pure follicle-stimulating hormone (PFSH)/human menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG). In 18 patients (group II), the protocol was identical to the former group, except for the addition of a short-acting GnRHa (buserelin) that was started when P levels were persistently high. The combination of long and short acting GnRH analogues (group II) resulted in an improved follicular phase with significantly lower P levels on the day of HCG administration (P less than 0.001). Furthermore, a significantly higher number of oocytes was retrieved, fertilized and cleaved (P less than 0.005; P less than 0.001; P less than 0.005, respectively) and, as a consequence, significantly higher pregnancy rates were achieved (22.2 versus 12.5%; P less than 0.005). These results indicate that a combination of long- and short-acting GnRH agonists may be of value in cases of persistent high P levels during menotrophin therapy in IVF cycles. Further larger studies must be performed before the true efficacy of this mode of treatment can be determined.

Adult↗
PubMed2000

Prednisone and aspirin improve pregnancy rate in patients with reproductive failure and autoimmune antibodies: a prospective study.

PROBLEM: The study was conducted to investigate the efficacy of prednisone and aspirin in autoantibody seropositive patients with repeated in vitro fertilization embryo transfer (IVF ET) failure. METHODS OF STUDY: The study group comprised 52 consecutive patients seropositive for non-organ-specific autoantibodies, i.e., anti-cardiolipin antibodies (ACA), anti-nuclear antibodies (ANA), anti-double-stranded (ds) DNA, rheumatoid factor (RF), and lupus anti-coagulant (LAC). These patients were treated with prednisone, 10 mg per day, and aspirin, 100 mg per day, starting 4 weeks before induction of ovulation in 52 IVF cycles. RESULTS: The clinical pregnancy rate per cycle was 32.7% (17/52). No increased incidence of pregnancy complications, including premature labor, gestational diabetes mellitus, and pregnancy-induced hypertension, were found. CONCLUSIONS: Combined treatment of prednisone for immunosuppression and aspirin as an anti-thrombotic agent, starting before ovulation induction, may improve pregnancy rate in autoantibody seropositive patients who have had repeated IVF-ET failures.

Antibodies, Anticardiolipin↗
PubMed1989

Evidence for a specific role of GnRH pulse frequency in the control of the human menstrual cycle.

An adequate frequency of gonadotropin-releasing hormone (GnRH) pulses appears to be important for physiological gonadotropin secretion. However, limited information exists on the exact role of this parameter in the regulation of the human menstrual cycle. Thus we studied gonadotropin and gonadal steroid secretion in 32 women with primary hypogonadotropic amenorrhea who received pulsatile GnRH (60 to 120 micrograms/day) at 60- or 120-min intervals for a total of 64 ovulation induction cycles. Ovulation was achieved in 94% of 60-min and in 70% of 120-min cycles P less than 0.05). In the follicular phase of ovulatory cycles, estradiol (E2) levels did not differ among the four groups; however, mean luteinizing hormone (LH) levels were lower (P less than 0.005), and the midcycle LH surge was severely blunted in cycles of subjects receiving 120 micrograms/day (5 micrograms/bolus) GnRH every 120 min compared with subjects receiving the same dose of GnRH per day or per bolus every 60 min. Luteal progesterone (only in 60 micrograms/day GnRH cycles) and E2 levels were lower in 120-min than in 60-min cycles (P less than 0.05). The use of the higher daily GnRH dose (120 micrograms/day) reduced or abolished the frequency-associated hormone level differences. We conclude that a low frequency of pulsatile GnRH in women 1) decreases mean LH levels and blunts the midcycle gonadotropin surge, 2) does not increase follicle-stimulating hormone concentrations, and 3) is associated with a reduced rate of ovulation.

Adult↗
PubMed1995

Recombinant FSH (Org32489) induces follicle growth and ovulation in the adult cyclic rat.

The effects of a single injection of recombinant human FSH (rhFSH; Org32489) on ovulation rate and timing and on antral follicle growth were studied in adult 5-day cyclic rats. Rats injected at 1700 h on dioestrus-2 with a dose of 10 IU rhFSH showed, on average, no increase in ovulation rate on the day of expected oestrus. However, an additional, precocious ovulation resulting in a normal number of corpora lutea (13.3 +/- 0.4, n = 6) was found to take place on the night after injection, i.e. dioestrus-3. No mating behaviour, as shown by the absence of vaginal plugs the next morning, was observed at this ovulation. Follicle counts showed a loss of large antral follicles due to ovulation and increased numbers of healthy small antral follicles at 17 and 41 h after injection, indicating a decrease of atresia of growing follicles as well as additional recruitment of new antral follicles. The endogenous serum FSH concentration on the subsequent day of oestrus (65 h after the rhFSH injection) as well as recruitment of small antral follicles were lower in the rhFSH-treated rats than in saline-treated controls. The ovulation at oestrus, 48 h after the precocious, rhFSH-induced ovulation showed large differences in the number of oocytes between the rats in one treatment group. Similar results in terms of immediate ovulation induction were obtained by using a highly purified human urinary FSH preparation (i.e. metrodin). Furthermore, the direct induction of ovulation by rhFSH or metrodin could not be prevented by the injection of an LHRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Canalization of human cervical mucus.

Cervical mucus forms channels when dried under a coverslip. The aim of the present work was: 1) to prove mucus canalization both in spontaneous ovulatory cycles and during ovulation induction with gonadotropins; 2) to prove the estrogen dependence of this phenomenon; 3) to check the importance of the proteidic and electrolytic concentration on chaneling; and 4) to use this phenomenon clinically, shortening the time in which it occurs. The number and arrangement of channels vary during the cycle. The phenomenon is estrogen-dependent. The comparison between estradiol values and the number of channels during spontaneous ovulatory cycles and treatment with gonadotropins showed a linear relationship. Treatment with estradiol 17 beta-valerate and ethinyl estradiol induced channel formation in women with primary amenorrhea. Canalization and ferning disappeared after dialysis or treatment with proteolytic enzymes. It follows that the two phenomena have similar characteristics. Canalization increases daily, as does estradiol, whereas ferning maintains the same grade for a longer period, and when a grade of + + + is reached, it provides no further indications. With the use of a thermostat, canalization occurred in only a few hours. Chaneling, a more precise index, could therefore substitute for ferning, particularly when monitoring the induction of ovulation.

Amenorrhea↗
PubMed1996

[Ovarian hyperstimulation syndrome--prevention and treatment].

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, potentially life-threatening condition associated with ovulation induction. With increasing numbers of women receiving various ovarian stimulation protocols as part of different infertility treatments, the number of cases is likely to increase. The syndrome has a wide spectrum of clinical and laboratory findings, and is classified into mild, moderate and severe OHSS. The pathophysiology of this syndrome is unclear, and medical management has traditionally been conservative and supportive consisting of bedrest, volume expanders and replacement of fluid. When ascites is present, paracentesis under ultrasound guidance has been found to improve the condition of the patient by reducing the hydrostatic pressure. Prevention is very important, but at present it is doubtful if OHSS can be completely avoided due to the existence of a relatively small margin of safety between successful induction of ovulation and the development of OHSS.

Female↗
PubMed2006

Fertility outcomes in women with hypopituitarism.

BACKGROUND: Women with hypopituitarism are known to have a poor outcome once pregnancy has been achieved by ovulation induction. There are no data, however, recording the efficacy of ovulation induction and pregnancy rates in this group of subfertile women. METHODS: The outcome of fertility treatments in all 19 women with hypopituitarism attending the fertility clinics of University College London Hospitals over the past 20 years was audited. RESULTS: Ovulation was achieved in almost all women (95%) but occurred in only 60% of treatment cycles. Pregnancy was achieved in 47% of women or 11% of cycles resulting in a live birth rate of 6.7% per cycle. Seven of the 18 pregnancies (39%) miscarried. Only 42% of women treated achieved a live birth. CONCLUSION: Ovulation induction in women with hypopituitarism yields relatively low pregnancy rates in comparison to other causes of anovulation and a high miscarriage rate. Pituitary hormone deficiency beyond gonadotrophins has a major adverse effect on achieving pregnancy.

Adult↗
PubMed1986

Induction of ovulation during anoestrus in two breeds of sheep with multiple injections of LH alone or in combination with FSH.

The gonadotrophic requirements for the induction of ovulation and formation of a viable corpus luteum in two breeds of seasonally anoestrous sheep of differing fecundity was investigated. Welsh Mountain (n = 20) and Damline ewes (n = 19) were given LH or FSH either alone or in combination. Luteinizing hormone was injected i.v. at an increasing frequency for 72 h (one injection every 3 h for 24 h, one every 2 h for 24 h, and one every hour for 24 h) and FSH was injected in an identical manner for the first 36 h of treatment. Exogenous LH alone and in combination with FSH induced a preovulatory LH surge in all 19 ewes and ovulation in 18 out of 19 ewes of both breeds. However exogenous FSH alone was ineffective. The incidence of normal corpus luteum function in ewes induced to ovulate was low and not related to treatment, timing or magnitude of the LH/FSH surge. It is concluded that in both breeds studied it is the infrequency of LH pulses which limits the development of preovulatory follicles during seasonal anoestrus, that the requirement for FSH remains unknown, and that the induction of inadequate corpora lutea during seasonal anoestrus reflects either defects in hormonal priming of the preovulatory follicle and/or inappropriate luteotrophic support after ovulation.

Anestrus↗
PubMedDate not supplied

Synchronous mucinous adenocarcinoma of the endometrium and mucinous cystadenoma of bilateral ovaries presenting during fertility therapy.

We describe a very rare case of synchronous mucinous tumor of the endometrium and ovaries presenting during ovulation induction. A 31-year-old woman received ovulation induction for 5-year primary infertility. Ultrasonography revealed mucus retention in the uterine cavity and bilateral multicystic ovaries during ovulation induction. Atypical hyperplasia was diagnosed by endometrial curettage. Repeated procedures including ovarian cystectomy, endometrial curettage and in vitro fertilization combined with progestine therapy resulted in no pregnancy but rapid recurrences. She finally underwent simple hysterectomy and bilateral salpingo-oophorectomy. Microscopic examination revealed mucinous cystadenoma in the both ovaries and well differentiated mucinous adenocarcinoma of the endometrium.

Adenocarcinoma, Mucinous↗
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↗
PubMed2004

Obstetric implications for and identification of women with a normal clomiphene citrate challenge test result who have a poor response to gonadotropins.

OBJECTIVE: To determine the incidence and obstetric implications and to identify prospectively women with a poor response to hMG with a normal clomiphene citrate challenge test (CCCT) result. DESIGN: Retrospective chart review. SETTING: Tertiary fertility center. PATIENT(S): One hundred sixty-three women who underwent ovulation induction with hMG for IUI, and 266 women who underwent ovulation induction with GnRH analogue and hMG for IVF. All had a CCCT before stimulation. Seventy-five percent of IUI patients (123 of 163) and 89% of IVF patients (238 of 266) had normal CCCT results. A poor response to hMG was defined as a response less than the 90th percentile of women with an abnormal CCCT result (peak E(2) [pg/mL] level per ampule hMG used: 90th percentile </=30). INTERVENTION(S): Clomiphene citrate challenge test and ovulation induction for IUI or IVF. MAIN OUTCOME MEASURE(S): Response to gonadotropins and pregnancy outcome after treatment. RESULT(S): Thirty-five percent of IUI patients (43 of 123) and 52% of IVF patients (123 of 238) with a normal CCCT result had a poor response to hMG. Intrauterine insemination patients with a poor response to hMG had significantly lower delivery rates than IUI patients with a normal response (19% vs. 39%). In vitro fertilization patients with a poor response to hMG had similar delivery rates compared with IVF patients with a normal response (32% vs. 35%). For both groups of patients, an FSH >12 mIU/mL (IMx assay) on either day 3 or day 10 (normal </=14.5 IMx) was highly predictive of a poor response to hMG, the elevated FSH level being a much better predictor than the woman's age. CONCLUSION(S): A poor response to hMG with a normal CCCT result (false negative) is a common event. A day-3 or day-10 FSH >12 mIU/mL (IMx assay) or 20 mIU/mL (converted to the original RIA) will identify approximately 80% (IUI) and approximately 94% (IVF) of the women who will experience a poor response to hMG. When identified, the data suggest that these patients will benefit significantly from the more aggressive IVF.

Adult↗
PubMed1994

Regulation of corpus luteum function.

The effects have been studied of different ovulation induction regimens [either clomiphene citrate or buserelin in combination with human menopausal gonadotrophin (HMG)] on the circulating concentrations of progesterone, oestradiol, relaxin and human chorionic gonadotrophin (HCG) during the first trimester of pregnancy. Ovulation induction with clomiphene resulted in elevated concentrations of gonadotrophins in both phases of the cycle, while during ovulation induction with buserelin, gonadotrophin concentrations were elevated in the follicular phase only. The concentrations of all corpus luteum products were greater in clomiphene pregnancies compared with spontaneous pregnancies, but only oestradiol and relaxin concentrations were greater in clomiphene pregnancies compared with buserelin pregnancies. The concentrations of HCG were significantly reduced in clomiphene pregnancies compared to natural pregnancies. Relaxin concentrations were significantly higher from 7 weeks gestation in buserelin compared with spontaneous pregnancies, while progesterone, oestradiol and HCG concentrations were not consistently different. Consistent associations were found between relaxin and HCG concentrations in spontaneous pregnancies and between the concentrations of relaxin and both progesterone and oestradiol in pregnancies achieved after ovulation induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗