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PubMed1993

Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome.

OBJECTIVE: To compare the effect of treatment with gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropins (hMG) with that of gonadotropins only, on the cumulative livebirth rate and miscarriage rate of pregnancies achieved in women with polycystic ovarian syndrome (PCOS). DESIGN: Retrospective analysis of the outcome of 97 pregnancies according to the treatment protocol, with or without GnRH-a. Calculation of miscarriage rate and cumulative livebirth rate by life-table analysis. SETTING: Infertility clinic and in vitro fertilization (IVF) unit. PATIENTS: Women with polycystic ovaries (n = 239) who were clomiphene citrate failures and received either GnRH-a/hMG (n = 110) or gonadotropins only (n = 129) for ovulation induction (n = 138) or superovulation for IVF (n = 101). INTERVENTIONS: For ovulation induction, hMG was given in a step-up, individually adjusted dose scheme. For IVF, three ampules of pure follicle-stimulating hormone were given for 3 days followed by three ampules per day hMG and then individual dose adjustment. Gonadotropin-releasing hormone agonist (Decapeptyl, D-Trp6, microcapsules, 3.75 mg) was given in a single dose 2 weeks before gonadotropin treatment. MAIN OUTCOME MEASURES: The rate of early miscarriages (< 12 weeks) per pregnancies achieved was analyzed, and the cumulative livebirth rate for each treatment group was calculated by life-table analysis. RESULTS: Miscarriage rates after treatment in ovulation induction with (16.7%) and without GnRH-a (39.4%) and in IVF with (18.2%) and without GnRH-a (38.5%) were almost identical and were therefore analyzed together. Of pregnancies achieved with GnRH-a, 17.6% miscarried compared with 39.1% of those achieved with gonadotropins alone. Cumulative livebirth rate after four cycles for GnRH-a was 64% compared with 26% for gonadotropins only. CONCLUSIONS: Cotreatment with GnRH-a/hMG for anovulatory women with PCOS reduces the miscarriage rate and improves the livebirth rate compared with treatment with gonadotropins alone.

Abortion, Spontaneous↗
PubMed2002

The impact of hormonal therapy for infertility on the age at menopause.

OBJECTIVES: To look for possible association between past history of ovulation induction and age at menopause. DESIGN: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. PATIENTS: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. RESULTS: The age at the final menstrual bleeding was 46.4+/-5 in the study group, and 50+/-4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8+/-5 years. Smoking had a weak effect on the age at menopause (48.5+/-4 for current, vs. 49.9+/-4 for non- or past-smokers; P<0.03). CONCLUSIONS: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.

Adult↗
PubMedDate not supplied

Bromocriptine for induction of ovulation in hyperprolactinemic amenorrhea.

Hyperprolactinemia is a frequent finding in infertile women with amenorrhea. Bromocriptine is the drug of choice for treatment of hyperprolactinemic amenorrhea. This dopamine agonist is very effective in normalizing raised prolactin levels. Ovulatory menstrual cycles and fertility are then rapidly restored. Bromocriptine therapy represents a major advance in the treatment of anovulatory infertility. Prolactin-secreting pituitary adenomas are common causes of hyperprolactinemia. Neither surgery nor irradiation reliably provides the definitive cure that had been hoped for in patients with prolactin-secreting pituitary tumours. Experience with medical treatment has revealed that induction of ovulation with bromocriptine is remarkably safe both in patients with microtumours and those with macrotumours without suprasellar extension. In the future, it is possible that even the larger macrotumours with suprasellar can be safely managed by medical therapy with bromocriptine. During pregnancy, pituitary tumour complications may arise in women with prolactinomas. However, data accumulated during recent years have shown that induction of ovulation and pregnancy by bromocriptine is remarkably safe in women with both micro- and macroprolactinomas. The risk of permanent sequelae due to rapid tumour enlargement during pregnancy is exceedingly small in properly investigated and carefully supervised women with prolactinomas. Bromocriptine is clearly a must for every infertility clinic. The value of bromocriptine in the treatment of normoprolactinemic amenorrhea, polycystic ovarian disease, luteal insufficiency and ovulatory infertility is not yet proven. However, bromocriptine is extremely effective in normalizing hyperprolactinemia and undoubtedly the drug of choice for treatment of female infertility due to hypersecretion of prolactin.

Adenoma↗
PubMed2005

Assisted reproductive technology and pregnancy outcome.

OBJECTIVE: To determine whether the use of assisted reproductive technology (ART) is associated with an increase in chromosomal abnormalities, fetal malformations, or adverse pregnancy outcomes. METHODS: A prospective database from a large multicenter investigation of singleton pregnancies, the First And Second Trimester Evaluation of Risk trial, was examined. Subjects were divided into 3 groups: no ART use, use of ovulation induction (with or without intrauterine insemination), and use of in vitro fertilization (IVF). Multivariate logistic regression analysis was used to assess association between ART and adverse pregnancy outcomes (significance of differences was accepted at P < .05). RESULTS: A total of 36,062 pregnancies were analyzed: 34,286 (95.1%) were spontaneously conceived, 1,222 (3.4%) used ovulation induction, and 554 (1.5%) used IVF. There was no association between ART and fetal growth restriction, aneuploidy, or fetal anomalies after adjustment for age, race, marital status, years of education, prior preterm delivery, prior fetal anomaly, body mass index, smoking history, and bleeding in the current pregnancy. Ovulation induction was associated with a statistically significant increase in placental abruption, fetal loss after 24 weeks, and gestational diabetes after adjustment. Use of IVF was associated with a statistically significant increase in preeclampsia, gestational hypertension, placental abruption, placenta previa, and risk of cesarean delivery. CONCLUSION: Patients who undergo IVF are at increased risk for several adverse pregnancy outcomes. Although many of these risks are not seen in patients undergoing ovulation induction, several adverse pregnancy outcomes are still increased in this group. There was no increased incidence of fetal chromosomal or structural abnormalities in the women who used any type of ART compared with the women who conceived spontaneously. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMedDate not supplied

Mono-ovulatory cycles: a key goal in profertility programmes.

Mono-ovulatory cycles for women are optimal because singleton pregnancies have a better outcome than multiples. Multiple births began to increase in the 1950s after the first appearance of effective ovulation induction for the treatment of anovulation. Since the 1980s when ovulation induction and IVF were more broadly applied to the treatment of unexplained and persistent infertility, there has been an unprecedented rise in multiple births. Strategies to achieve mono-ovulation during treatment of anovulatory patients are distinct from those for the treatment of ovulating patients who have unexplained and persistent infertility. Anovulatory patients with hypogonadotrophic hypogonadism can be treated with exogenous pulsatile GnRH, which restores normal gonadotrophin secretion, ovulation rates and conception rates. The multiple pregnancy rate is not increased with GnRH treatment. In patients with normogonadotrophic anovulation, attention should be given to diet and exercise before any other interventions are considered. Pharmacological induction of ovulation can be achieved with antiestrogen, gonadotrophin or pulsatile GnRH treatment; antiestrogen is the first choice with gonadotrophin more widely used for clomiphene citrate (CC)-resistant patients. Obesity and polycystic ovaries are common in this group, so that gonadotrophin and GnRH treatment are associated with lower responses compared with hypogonadotrophic hypogonadism, and higher multiple pregnancy rates. Low dosage protocols are being tested that may lower the multiple birth rates. The role of drugs enhancing sensitivity to insulin, e.g. metformin, remains undetermined. Laparoscopic ovarian diathermy achieves conception rates that are equivalent to gonadotrophin treatment, with fewer multiple births. Augmenting normal ovulation processes for couples with unexplained and persistent infertility is less effective. Pregnancy rates are statistically significantly higher with CC but the size of the increase is not clinically important. CC with intrauterine insemination is associated with a clinically important effect on conception. Achieving mono-ovulation is more difficult in assisted reproductive technology cycles because success depends on maintaining the level of FSH above the threshold level longer than normal in order to increase the number of mature follicles. Milder stimulation for IVF and IVF in the untreated cycle show great potential, however, especially in view of the trend toward transfer of a single embryo in assisted reproductive treatment cycles.

Anovulation↗
PubMed2000

Ovarian stimulation in a woman with premature ovarian failure and X-autosome translocation. A case report.

BACKGROUND: There are only a few reports on ovulation induction in women with premature ovarian failure resulting from an X chromosome abnormality. Up to now, there have been no publications on ovulation stimulation in a patient with an X-autosome translocation. CASE: A healthy, 29-year-old woman had premature ovarian failure (POF) but no other discernible pathologic clinical features. Laboratory tests prior to initiating a stimulation cycle revealed a 46,XX t(X;16) karyotype. Genetic counseling was proposed, and the risk of X chromosome abnormality was discussed. The couple decided to undergo ovulation induction. For treatment of infertility, clomiphene citrate had been administered in the past. Because those treatments were not successful, GnRH-a and follicle stimulating hormone treatment was recommended. The first treatment cycle was successful in inducing ovulation, but on the 15th day after human chorionic gonadotropin administration, menstruation occurred. The couple refused a second stimulation, and menstruation occurred 32 days after the first. The patient then became amenorrheic again. CONCLUSION: At least some hope can be offered to infertile women with hypergonadotropinism and X-autosomal translocation, although it is impossible to determine whether ovulation induction will result in pregnancy. New treatments can be anticipated for women with POF and X chromosome aberrations who have similar hormonal environments.

Adult↗
PubMed1989

[Changes in serum FSH, LH and ovarian follicular growth during electroacupuncture for induction of ovulation].

Changes in serum FSH, LH and follicular sizes were observed in chronically anovulatory patients during electroacupuncture treatment (EAT) for induction of ovulation. 7 cases were diagnosed as PCOD, 3 as dysfunctional uterine bleeding, and 1 as hypogonadotropic amenorrhea. Among them 8 cases complained of infertility for 2.7 years on average. Ovulation was confirmed by pregnancy or the combination of biphasic BBT and ultrasonographic evidence. During one cycle with 3-day EAT on acupoints Ren 3, 4, Extra 16 and Sp 6, ovulation resulted in 5 patients (ovulatory group) and among the 5 cases, 3 of 4 infertile cases became pregnant. The other 5 cases remained in anovulation (anovulatory group); of them 3 cases got biphasic BBT, but no typical ovulatory signs were found on ultrasonography; 2 cases remained in monophasic BBT. Serum FSH, LH values were elevated in ovulatory group, and FSH pulsatile frequency increased significantly during EAT (from 2.10 +/- 0.42/4h to 3.70 +/- 1.64/4h), but not in anovulatory group. No apparent changes were found in serum LH pulsatile frequency and pulsatile amplitudes of FSH and LH in this study. In ovulatory group diameters of ovarian follicles increased markedly, while diameters of anovulatory group stopped to grow at 14-16 mm. It is suggested that ovulation may be induced by EAT via a regulation on hypothalamic-pituitary function leading to normal secretion of FSH and LH.

Acupuncture Therapy↗
PubMed1996

Down's syndrome screening marker levels following assisted reproduction.

Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Biomarkers↗
PubMedDate not supplied

The effects of indoleamines (serotonin and melatonin) on induction of ovulation in rabbits.

Serotonin as well as melatonin introduced into the 3-rd cerebral ventricle in doses of 120 mug blocked induction of ovulation in rabbits; it was also observed that the ovulation-blocking effect of serotonin was much more effective than that of melatonin. The inhibitory effect of both indolamines on this process was more evident in summer than in spring. The role of serotonin and melatonin as mediators blocking the release of hypothalamic gonadotropin-releasing hormones (GRH) and the participation of these amines in the regulation of seasonal sexual rhythms are discussed.

Animals↗
PubMed2001

How to avoid multiple pregnancies in assistive reproductive technologies.

Since 1980, there has been a worldwide dramatic increase in multiple births. This seems to be due to an increase in the age of reproduction, the use of ovulation induction, and the use of in vitro fertilization. Scarce data suggest that each of these causes is responsible for about one-third of the problem, although quintuplets and more are almost invariably due to ovulation induction. There has been little or no effort to issue guidelines or regulations with respect to ovulation induction, but there has been much advice as to how to control the problem in in vitro fertilization by limiting the number of embryos to be transferred. In sum, a good selection of high-quality embryos on day 3 would allow a high rate of pregnancy with the transfer of one or two blastocysts. Good results of cryopreservation must be part of an agreement in an in vitro fertilization program. If singleton live birthrates were considered to be the principal outcome of assisted reproductive technologies reported by centers and registry, twin and triplet rates should also be reported separately. And finally, if financial considerations would not limit the cost of reimbursement to in vitro fertilization procedures, the number of procedures could be increased with fewer embryos transferred.

Adult↗
PubMed1993

The effect of fertility drugs and in vitro methods on the outcome of 106 triplet pregnancies.

OBJECTIVE: To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. DESIGN: Prospective clinical study. SETTING: A single university medical center. PATIENTS: One hundred six consecutive triplet pregnancies treated from 1984 through 1992. MAIN OUTCOME MEASURES: The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. RESULTS: Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25 weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. CONCLUSION: Triplet pregnancies after ovulation induction and IVF have a similar outcome.

Adult↗
PubMed1998

Ovarian stimulation with low-dose pure follicle-stimulating hormone in polycystic ovarian syndrome anovulatory patients: effect of long-term pretreatment with gonadotrophin-releasing hormone analogue.

A randomised clinical trial was performed to evaluate the effect of a 3-month gonadotrophin-releasing-hormone analogue (GnRH-a) in one cycle of ovulation induction with low-dose pure follicle-stimulating hormone (pFSH) in patients with polycystic ovarian syndrome (PCOS) anovulation. Twenty patients with chronic anovulation due to PCOS were randomised to ovulation induction with pFSH administered in a low-dose schedule with (10 patients) and without (10 patients) a 3-month pretreatment with GnRH-a. Ultrasound scan only monitoring of follicular growth, evaluation of plasmatic oestradiol at the day of triggering of ovulation with human chorionic gonadotrophin 5,000 IU and evaluation of plasmatic progesterone 8 days after were the main outcome measures. Ovulation occurred in 9 patients treated with pFSH and in 2 patients treated with GnRH-a plus pFSH. Five pregnancies in the pFSH group and no pregnancy in the GnRH-a group were obtained. Five cycles were stopped due to multifollicular growth in the GnRH-a group and 1 in the pFSH group. Pretreatment with a 3-month administration of a GnRH-a did not improve the ovulation rate and pregnancy rate in PCOS patient ovulation induction with low-dose pFSH.

Adult↗
PubMed1976

Effect of clomid, sexovid and prostaglandins on induction of ovulation and gonadotropin secretion in a freshwater catfish, Heteropneustes fossilis (Bloch).

The effect of clomid, sexovid and some prostaglandins (PGE1 and PGF2alpha) on the induction of ovulation, ovarian activity and gonadotropin concentration in the pituitary and blood serum was studied in H. fossilis. Sham-hypophysectomized individuals recorded a very high percentage (90--100%) of ovulation on the 6th day of clomid (150 mug), sexovid (150 mug), PGE1 (100 mug) and PGF2alpha (100 mug) administration. Amongst hypophysectomized recipients only sexovid treated ones ovulated (78%). These drugs were very effective in promoting the ovarian activity in intact specimens but, except sexovid, failed to stimulate any response in hypophysectomized subjects. The gonadotropin concentration in the pituitary gland and blood serum was also elevated after the treatment with the above compounds. It is quite evident from the data that clomid, PGE1, and PGF2alpha, probably acting via hypothalamus, accelerate the synthesis and release of gonadotropin which in turn induces hightened ovarian activity resulting in ovulation. Sexovid seems to have twofold action-- the one indirect through hypothalamus leads to hypophysis leads to ovary like clomid and prostaglandins, and the other directly upon the ovary, possibly by increasing its response to the available gonadotropin, or by behaving like LH.

Animals↗
PubMed2005

Prolactin inhibits oocyte release after gonadotropin stimulation in the rat: putative mechanism involving ovarian production of beta-endorphin and prostaglandin.

OBJECTIVE: To evaluate whether prolactin (PRL) is able to inhibit ovulation induced with exogenous gonadotropins in the rat and whether this effect could be mediated by the ovarian production of beta-endorphin, prostaglandin, and nitric oxide (NO). DESIGN: Controlled in vivo and in vitro experiments. SETTING: Academic research laboratories. ANIMAL(S): Immature female rats undergoing ovulation induction with equine gonadotropins and hCG. INTERVENTION(S): Prolactin (100 or 200 microg), PRL + the opioid antagonist naloxone (200 microg each), or placebo were injected SC 4 hours after hCG administration for ovulation induction. In the in vitro experiments, isolated preovulatory ovaries were incubated with or without PRL in a final concentration of 100 or 200 ng/mL. MAIN OUTCOME MEASURES(S): Number of oocytes ovulated in vivo, ovarian beta-endorphin, PGE(2) and NO(2)(-)/NO(3)(-) release, and NO synthase activity in vitro. RESULT(S): Prolactin reduced significantly the number of oocytes ovulated at the doses of 100 and 200 microg, and this effect was partially reversed by naloxone administration together with 200 mug PRL. PRL also induced a twofold increase in the ovarian release of beta-endorphin and a threefold decrease in the ovarian production of PGE(2). Ovarian NO synthase activity and the concentrations of NO(2)(-)/NO(3)(-) in the incubation medium were not modified by PRL. CONCLUSION(S): Prolactin is able to reduce the number of oocytes released and modulate ovarian beta-endorphin and PGE(2) release, which may account for its peripheral anovulatory effects. This local effect of PRL could interfere in the process of ovulation induction by exogenous gonadotropins.

Animals↗
PubMed1995

Fertility therapy in the setting of a history of invasive epithelial ovarian cancer.

A link between fertility drugs and epithelial ovarian cancer has been suggested by at least one case-control study, and by multiple case reports of such tumors developing following fertility drug therapy. We report the case of a woman with stage IC grade 1 mucinous epithelial ovarian cancer who died of recurrent disease shortly after receiving gonadotropin therapy for ovulation induction. The patient was initially treated with a staging procedure, unilateral salpingo-oophorectomy, and 3 courses of cytoxan and carboplatinum. Over the next 3 years she underwent 2 cycles of ovulation induction with exogenous gonadotropins. Five months after the second cycle, the patient presented with a bowel obstruction and extensive recurrence of disease. Two months later she died despite extensive surgical debulking, and cis-platinum and Taxol chemotherapy. Although a causal relationship between fertility therapy and ovarian cancer has not been established, this case report suggests ovulation induction may be inadvisable in a woman with a prior diagnosis of invasive epithelial ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed1999

Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea.

OBJECTIVE: To assess the effect of supplementing an ovulation induction regimen of highly purified FSH with LH activity in the form of low-dose hCG therapy. DESIGN: Case report. SETTING: The Reproductive Endocrinology Center at the University of Bologna, Bologna, Italy. PATIENT(S): A woman with weight-related secondary hypogonadotropic amenorrhea. INTERVENTION(S): The patient was treated first with highly purified FSH alone and then received highly purified FSH in combination with low-dose hCG therapy (50 IU/d). MAIN OUTCOME MEASURE(S): Pelvic ultrasound examinations, serum E2 levels, duration of treatment, total dose of highly purified FSH, and outcome of treatment. RESULT(S): The concomitant administration of low-dose hCG and highly purified FSH markedly reduced the duration of treatment and the dose of highly purified FSH, and resulted in a quadruplet pregnancy in a patient in whom several previous ovulation induction procedures had been unsuccessful. CONCLUSION(S): Supplementation of an ovulation induction regimen with an agent that has LH activity can enhance FSH-induced folliculogenesis and markedly reduce costs in women with hypogonadotropic hypogonadism. However, this increased response can be associated with complications such as multiple gestation.

Adolescent↗
PubMed1984

Induction of ovulation with an estrogen antagonist, tamoxifen.

Tamoxifen (Norvadex), synthesized by the Imperial Chemical Industries Ltd., is a triphenylethylene derivative having a clomiphene-like structure and displays anti-estrogenic activities. In this study we used tamoxifen for the treatment of anovulatory infertility and investigated the clinical results. Induction rate of ovulation recorded 100% in the patients with sporadic anovulatory cycle, 83.3% in those with persistent anovulatory cycle, 70% in those with the first grade amenorrhea type I and 66.7% in those with the first grade amenorrhea type II. However, tamoxifen was absolutely ineffective against the second grade amenorrhea. The patients with sporadic or persistent anovulatory cycle responded to 40 mg-daily tamoxifen-treatment, recording 100% of ovulatory induction rate. The patients with the first grade amenorrhea also responded to 60 mg-daily treatment, indicating 70% of ovulatory induction rate. The rate of pregnancy established in the women desiring pregnancy marked 15.4%, and 2 out of 4 women with successful pregnancy experienced spontaneous abortion. Out of 4 patients who did not respond to the previous clomiphene treatment, 3 women accomplished ovulatory induction with tamoxifen. The endocrinological dynamics in the tamoxifen treatment were similar to those in the clomiphene treatment.

Amenorrhea↗
PubMed1988

Gamete intrafallopian tube transfer (GIFT): making laparoscopy more than "diagnostic".

Diagnostic laparoscopy is commonly performed on patients as part of a complete infertility investigation. Recently published protocols have investigated the efficacy of using empiric ovulation induction, intrauterine insemination, or both before beginning in vitro fertilization. Because many patients enrolled in these protocols will be exposed to both ovulation induction and diagnostic laparoscopy, the authors reasoned that it would be more effective to begin ovulation induction at the time of the proposed diagnostic laparoscopy in order to allow gamete intrafallopian tube transfer (GIFT) at the same time. Twenty-five nulliparous patients underwent diagnostic GIFT. There were eight continuing pregnancies in this group (32%). Diagnostic GIFT is a more effective use of the opportunity provided by laparoscopy than diagnostic laparoscopy alone.

Adult↗