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PubMedDate not supplied

Ovulation induction increases serum levels of insulin-like growth factor binding protein 1.

The effect of ovulation induction on serum insulin-like growth factor binding protein 1 (IGFBP-1) level in relation to sex hormone binding globulin (SHBG) levels was evaluated. Serum samples were collected 8 to 12 days after ovulation from 26 women undergoing ovulation induction with clomiphene citrate (CC), and from 58 women treated with CC in combination with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). In addition, serum samples were obtained from 63 spontaneously ovulating women and from 12 women during an anovulatory cycle. Luteal phase serum IGFBP-1 levels were 4.22 +/- 2.95 micrograms/L (P less than .05) in the CC group and 7.31 +/- 6.13 micrograms/L (P less than .001) in the CC/hMG/hCG group as compared to unstimulated ovulatory cycles (2.64 +/- 2.52 micrograms/L). No significant difference in IGFBP-1 levels was seen between spontaneously ovulatory and anovulatory cycles. The serum IGFBP-1 levels correlated positively to SHBG levels (r = .52, P less than .001). The data show that ovulation induction increases serum IGFBP-1 levels in parallel to SHBG levels, indicating that ovarian stimulation, which results in increased steroid hormone production, also induces changes in other factors known to modulate steroid hormone actions.

Anovulation↗
PubMed2001

Synchronous endometrioid carcinoma of the ovary and endometrium associated with ovulation induction.

Over the last 2 decades great concern about the possible association between ovarian cancer and ovulation induction has been raised. Between the first reported case in 1982 and the end of year 2000, there have been 44 cases of ovarian carcinoma reported to occur in women previously treated with ovulation induction drugs. Most of these tumors were of the serous type with low malignant potential. In the present case, the patient had secondary anovulatory infertility and previous left cystoophorectomy for ovarian endometrioma. She was treated with human menopausal gonadotrophin alone or in combination with clomiphene citrate for 13 cycles prior to presentation. Screening ultrasound revealed multicystic right ovarian mass (15 x 9 x 6 cm). Hysterectomy and right salpingo-oophorectomy were carried out. Intraoperative and histological examinations showed stage 1A endometrioid ovarian cancer and well-differentiated endometrial adenoacanthoma with minimal myometrial invasion. A brief but critical review of published literature regarding the association of ovulation induction and increased risk of ovarian cancer is presented.

Adenocarcinoma↗
PubMed2005

Review: aromatase inhibitors for ovulation induction.

CONTEXT: For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. EVIDENCE ACQUISITION: We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. CONCLUSIONS: Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.

Anovulation↗
PubMed1992

Ovulation induction in women age 40 and older: the importance of basal follicle-stimulating hormone level and chronological age.

OBJECTIVES: To determine pregnancy and livebirth rates for women age 40 and older undergoing ovulation induction and to assess the impact of basal follicle-stimulating hormone (FSH) on outcome in these patients. DESIGN: Prospective, observational. SETTING: Fertility service of university medical center. PATIENTS: Infertile couples in whom the female partner was age 40 or older referred for ovulation induction therapy. INTERVENTION: Assessment of basal hormonal status; ovulation induction. MAIN OUTCOME MEASURES: Clinical pregnancy rate (PR), livebirth rate. RESULTS: Analysis of 402 cycles in 85 women age 40 and older demonstrated a clinical PR of 3.5% per cycle (95% confidence interval [CI] 1.7% to 5.3%). The livebirth rate was 1.2% per cycle (95% CI 0.1% to 2.3%). Women with a basal FSH < 25 IU/L and age < 44 years had a clinical PR of 5.2% per cycle (95% CI 2.5% to 7.9%) compared with 0.0% per cycle (95% CI 0.0% to 2.1%) in cases in which either basal FSH was > or = 25 IU/L or age was > or = 44 (P < 0.005). The prognostic importance of basal FSH and chronological age was confirmed by multivariate logistic regression analysis. The predictive value of the resulting regression equation was high (R2 = 0.94; P < 0.01). CONCLUSIONS: Pregnancy and livebirth rates are generally low during ovulation induction in women age 40 and older. In combination, basal FSH and chronological age are accurate predictors of PR, in these couples and can define a subset of patients with a more favorable prognosis. The spontaneous abortion rate in women who do conceive is high, substantially lowering the livebirth rate.

Adult↗
PubMed1994

Systemic lupus erythematosus induced by ovulation induction treatment.

Infertile women are treated with various regimens for ovulation induction. The ultimate end-result of these treatments is a significant rise in levels of serum gonadotropins and estradiol--the most potent natural estrogen. Estrogens may affect diverse biologic functions, including immune and inflammatory reactions. A role for estrogens in the development or exacerbation of systemic lupus erythematosus (SLE) has been suggested by many studies. In this report, we present 3 cases of otherwise healthy women who received ovulation induction agents and subsequently developed full-blown SLE. The possible association between this treatment and SLE is discussed.

Adult↗
PubMed1999

Ovarian cancer and ovulation induction drugs--is there a link?

Screening for ovarian cancer in a group of women with induced ovulations was encouraged by recently reported controversies about a possible association between the use of ovulation induction drugs and the increased risk of ovarian carcinoma. Transvaginal color Doppler ultrasonography was applied in screening for early stage ovarian malignoma in 110 asymptomatic women who received an ovulation induction therapy for infertility. Already reported standard parameters for discriminating malignant from benign flows, such as resistance index RI < 0.40, pulsatility index PI < 1 and morphological score (borders, cyst quality, septate areas, papilla and ovarian tissue echogenicity) were used. Screening included 110 women and was carried out from April 1, 1198 to March 31, 1999. Seven examinees had abnormal ovarian findings. The finding spontaneously regressed in five of them, one underwent surgery for a persistent cyst with a benign pathohistologic diagnosis, and one was diagnosed with early stage ovarian malignoma. RI < 0.40 was reported in one patient (0.9%) with a morphologically suspect finding and a pathohistologically confirmed malignoma, PI < 1 was found in 40 subjects or 36.4%, while malignoma was demonstrated in one case alone. The results showed the advantage of RI over PI in discriminating malignant from benign structures. The association between the use of ovulation stimulation drugs and the increased risk of ovarian carcinoma remains unproved and also challenges new dilemmas. The paper cautions against undesirable, potentially serious long-term effects of the use of ovulation induction agents. Additional trials should therefore be performed including a long-term prospective follow-up of women with induced ovulations.

Adult↗
PubMed2000

Induction of final follicular maturation and early luteinization in women undergoing ovulation induction for assisted reproduction treatment--recombinant HCG versus urinary HCG. The European Recombinant Human Chorionic Gonadotrophin Study Group.

This multicentre, double-blind, double-dummy, randomized, parallel-group study compared the efficacy and safety of recombinant human chorionic gonadotrophin (rHCG) (Ovidrel((R))) and urinary HCG (uHCG) (Profasi((R))) for inducing final follicular maturation and early luteinization in women undergoing ovulation induction for assisted reproduction treatment. Following long down-regulation and stimulation with recombinant human FSH (rFSH) (Gonal-F((R))), a total of 190 women received a single, s.c. injection of either 250 microg rHCG or 5000 IU uHCG. For evaluable patients (n = 172), the mean number of oocytes retrieved per patient (primary efficacy endpoint) was 11.6 for rHCG and 10.6 for uHCG (not significant). The mean number of mature oocytes was statistically higher (P = 0.027) for the rHCG group than the uHCG (9.4 versus 7.1). Serum progesterone concentrations on day 1 and days 6-7 post-HCG, and serum HCG concentrations at all post-HCG time points were statistically significantly in favour of rHCG. The clinical pregnancy rate was somewhat higher (not significant) in the rHCG group (33 versus 25%) as was the live birth rate (27 versus 23%, not significant). Both treatments were well tolerated, though the incidence of adverse events was significantly higher in the uHCG group (45.1 versus 22.7%, P = 0.0004). The incidence of injection-site reactions was significantly lower in the rHCG group (P = 0.0001). In conclusion, for triggering ovulation, rHCG seems to have significant advantages compared with uHCG in terms of number of mature oocytes retrieved, luteal progesterone and local tolerance.

Adult↗
PubMed1992

The appearance of one-pronuclear human oocytes is associated with a better ovulation-induction response and successful pregnancy outcome.

OBJECTIVE: To study the relationship between the presence of one-pronuclear oocytes in in vitro fertilization (IVF) patients and ovulation-induction response, oocyte and embryo development, and clinical outcome. DESIGN: Retrospective analysis of 535 consecutive IVF retrievals. Retrievals in which one or more oocytes exhibited one pronucleus were compared with retrievals in which no one-pronuclear oocytes (control) were observed. The following one-pronuclear versus control subgroups were also examined: leuprolide acetate/human menopausal gonadotropin (LA/hMG) ovulation inductions, high estradiol (E2) response cases, and retrievals in which a large number of oocytes (greater than or equal to 15) were recovered. SETTING: Brigham and Women's Hospital, a tertiary care, university-affiliated hospital. PATIENTS: Three hundred forty-six IVF patients were treated between January 1989 and May 1991. MAIN OUTCOME MEASURES: Parameters examined included E2 concentration and number of follicles with maximum diameter greater than or equal to 12 mm on day of human chorionic gonadotropin administration; number of total and mature oocytes retrieved; total fertilization rates; number of embryos; and percent per retrieval of embryo transfers (ETs), clinical pregnancies, and ongoing-livebirths. RESULTS: The one-pronuclear patients had higher E2 levels and larger number of follicles, yielded significantly more total and mature oocytes, had a higher overall fertilization rate, produced more embryos, and had higher ET, clinical pregnancy and ongoing-livebirth rates per retrieval than did the control patients. Analysis of the subgroup populations revealed no significant differences in the majority of the main outcome measures studied; however, the one-pronuclear patients yielded significantly more total and mature oocytes per retrieval. CONCLUSIONS: Although there was an increase in the clinical and ongoing-livebirth pregnancy rates (PRs) in one-pronuclear patients, this was probably associated with an improved ovulation-induction response in the one-pronuclear patients. They achieved significantly higher E2 levels, recruited a larger number of follicles, and yielded more oocytes and embryos per retrieval than the control patients. When only the LA/hMG, E2 greater than or equal to 1,500 pg/mL, or the greater than or equal to 15 oocytes/case retrievals were analyzed, the PRs were no longer different; however, the one-pronuclear patients still yielded significantly more total and mature oocytes per retrieval than the controls. Therefore, the appearance of one-pronuclear oocytes is probably associated with the maturation stage of the oocytes obtained and is indicative of an ovulation induction in which a large number of preovulatory, metaphase II oocytes have been recruited.

Cell Nucleus↗
PubMed2005

Treatment preferences and trade-offs for ovulation induction in clomiphene citrate-resistant patients with polycystic ovary syndrome.

OBJECTIVE: To investigate patient preferences and trade-offs for laparoscopic electrocautery of the ovaries relative to ovulation induction with recombinant FSH (rFSH) in patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). DESIGN: Assessment of preferences and trade-offs in a randomized controlled trial. SETTING: Academic hospital. PATIENT(S): Thirty-two CC-resistant patients with PCOS who had been randomly assigned to either laparoscopic electrocautery of the ovaries or ovulation induction with rFSH and 32 control patients with PCOS under treatment with CC. INTERVENTION(S): Preference for laparoscopic electrocautery relative to rFSH was established during an interview. Trade-offs between treatment burden and effectiveness were evaluated by varying hypothetical pregnancy rates after laparoscopic electrocautery until patients switched in their initial preference. MAIN OUTCOME MEASURE(S): Preference for laparoscopic electrocautery of the ovaries; trade-off between burden and effectiveness of treatment. RESULT(S): The majority of the patients would prefer electrocautery of the ovaries over ovulation induction with rFSH if both treatment strategies resulted in similar pregnancy rates. However, most patients were willing to trade off their preference for increased effectiveness: the percentage of patients who preferred electrocautery over rFSH sharply declined when the difference in hypothetical pregnancy rates was more than 5% in favor of rFSH. CONCLUSION(S): Patients with polycystic ovary syndrome are well able to express an informed preference for laparoscopic electrocautery of the ovaries or ovulation induction with rFHS. Preferences are guided by features of the respective treatments but seem to be dominated by their effectiveness and safety.

Clomiphene↗
PubMed2003

[Ovulation induction therapy and systemic lupus erythematosus].

Improvement in the prognosis of SLE prognosis has led to considering infertility therapy. The earliest reports displayed complications such as SLE revealed by ovulation induction or thrombophlebitis. Fertility is known to be normal in women with SLE, excepting amenorrhea accompanying severe flare-ups, renal insufficiency-related hypofertility and ovarian failure secondary to cyclophosphamide therapy. Anti-phospholipid antibodies are suspected to cause defective nidation and placental ischemia. An exponential rise of serum estradiol is observed irrespective of the ovulation induction protocol used, leading to SLE flare-up and thrombosis. We have experience with 114 cycles in 21 women with SLE and/or APS. A complication (fetal loss, SLE flare-up, thrombophlebitis) revealed the underlying disease in 8 women. Eighteen pregnancies led to 9 live-births, 4 fetal deaths and 5 embryonic losses. Pregnancy rate was higher after ovulation induction using gonadotropins (25% per cycle), than clomiphene (4%). Pregnancy rate was similar after IVFETE, whether the protocol was planned or not. However, three-quarters of the pregnancies after unplanned IVFETE led to abortions. On the contrary, 6 out of 7 pregnancies after planned IVFETE led to live-births. Two women developed thrombophlebitis after gonadotropins therapy. A SLE flare-up appeared after 13 out of 62 cycles, with a flare-up rate higher after gonadotropins (27% per cycle) than clomiphene therapy (6%), and after an unplanned (30%) than a planned procedure (10%). In conclusion, ovulation induction therapy can reveal SLE or APS. Clomiphene complications are uncommon. When gonadotropin therapy is considered, a preventive anti-inflammatory therapy should be discussed in SLE patients, in conjunction with heparin and/or anti-aggregate therapy for those with asymptomatic anti-phospholipid antibodies or prior thrombotic events.

Adult↗
PubMed2002

VEGF plasma pattern in ovulation induction: evidence for an episodic secretion and lack of immediate effect of hCG.

Vascular endothelial growth factor (VEGF) is a potent stimulator of vascular proliferation and permeability. Ovarian granulosa cells have been identified as a major source of the cytokine and r-hCG was able to stimulate VEGF mRNA expression in vitro. In this study we have investigated the immediate effect of ovulation induction with hCG on peripheral VEGF levels in 6 women with primary infertility enrolled in the IVF/ET program. The patients underwent a 24-hour continuous blood withdrawal with sampling intervals of 15 minutes starting from 5 hours before ovulation induction with 10.000 IU hCG. Ovulation induction with hCG had no significant immediate effect on mean peripheral VEGF levels. However, VEGF plasma levels did exhibit significant episodic fluctuations with rapid increases every 90-120 minutes without any relation to circulating hCG levels. Taken together, the results of this study suggest that VEGF is released episodically and that systemic VEGF levels are not acutely altered by ovulation induction with hCG.

17-alpha-Hydroxyprogesterone↗
PubMed1993

A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction.

OBJECTIVE: To assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy. DESIGN: A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued. RESULTS: The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects. CONCLUSION: Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy.

Adult↗
PubMed1992

Growth hormone (GH)-binding protein regulation by estrogen, progesterone, and gonadotropins in human: the effect of ovulation induction with menopausal gonadotropins, GH, and gestation.

The recently described serum GH-binding protein (GH-BP) may reflect the GH-receptor level. To assess the serum GH-BP levels under various physiological and supraphysiological levels of sex steroids, we have evaluated its concentration in 26 patients undergoing 34 cycles of ovulation induction with either human menopausal gonadotropins (hMG)/hCG or GH/hMG/hCG. The latter ovulation induction protocol was undertaken in "Clonidine negative" patients in a prospective, randomized, crossed-over manner, between GH/hMG/hCG or hMG/hCG. The increase in GH-BP levels in patients' sera undergoing ovulation induction directly correlated with peripheral estradiol (E2) (r = 0.577; P < 0.001), and with peripheral progesterone (P4) (r = 0.542; P < 0.001; n = 174) concentrations in hMG/hCG cycles, and also in GH/hMG/hCG cycles (r = 0.669, P < 0.001 for E2, and r = 0.722, P < 0.001 for P4, n = 84). GH-BP levels did not change significantly in response to 0.15 mg Clonidine ingestion. The baseline GH-BP levels significantly correlated with the body mass index of 47 patients (r = 0.547; P < 0.001). The insulin-like growth factor-I (IGF-I) concentrations increased in correlation with increasing E2 levels up to 5500 pmol/L but decreased thereafter, at very high E2 concentrations. In gestations generated by ovulation induction with hMG/hCG or GH/hMG/hCG, longitudinal measurements of GH-BP levels showed an initial sharp increase during early gestation, followed by a gradual decrease beginning around the end of the first trimester and continuing during the mid and late trimesters. In normal spontaneous pregnancies, GH-BP levels, measured from the fifth week until term, were negatively correlated with gestational age (r = -0.581; P < 0.001; n = 84). This pattern is highly suggestive of the possibility that GH-BP is coregulated not only with E2 and P4 but also with hCG, and possibly other gonadotropins as well. Indeed, in patients with "resistant ovaries", pharmacological amounts of hMG failed to increase E2 concentrations but moderately increased GH-BP levels. These data provide good indirect evidence for coregulation of the GH-BP with both sex steroids and gonadotropins. The mid and late trimesters decrease in GH-BP levels in spite of increasing sex steroids concentrations, may be attributed to the decreasing hCG concentrations, and/or to the increasing secretion of placental lactogen (PL) and placental GH with the advancing gestation.

Carrier Proteins↗
PubMedDate not supplied

Current and future status of ovulation induction in polycystic ovary syndrome.

Great progress had been achieved during the last 20 years in the field of ovulation induction in patients with polycystic ovary syndrome (PCOS). Clomiphene citrate remains the first line of treatment for all anovulatory women with PCOS, since in properly selected patients the cumulative pregnancy rate approaches that in normal women. Human urinary gonadotrophins have been used extensively for ovulation induction, but the development of low-dose regimens has opened a new era in the management of anovulation related to PCOS. This article discusses the main advantages and disadvantages of the principal methods and regimens currently used for ovulation induction in patients with PCOS including clomiphene citrate, gonadotrophins, pulsatile gonadotrophin-releasing hormone (GnRH) and GnRH agonists. It also discusses new drugs discovered recently, particularly recombinant gonadotrophins and GnRH antagonists, and provides some thoughts regarding their use in future protocols. Finally, based on the discovery of new ovarian substances which specifically control luteinizing hormone (LH) secretion, this article develops assumptions on possible implications of these substances in the pathophysiology of PCOS and their potential use in the management of the syndrome.

Anovulation↗
PubMed2005

Predicting ongoing pregnancy following ovulation induction with recombinant FSH in women with polycystic ovary syndrome.

BACKGROUND: Ovulation induction with recombinant FSH (rFSH) is common in women with polycystic ovary syndrome (PCOS) not responding to clomiphene citrate treatment, despite the associated risk of multiple pregnancies. We analysed clinical, ultrasonographic and endocrine parameters during initial screening of women with clomiphene citrate-resistant PCOS as predictors of ongoing pregnancy within 12 months of treatment following ovulation induction with rFSH. METHODS: Eighty-five women were allocated to receive rFSH as part of a multicentre clinical trial. rFSH was administered in a chronic low-dose step-up protocol. The primary end-point was an ongoing pregnancy within 12 months. A logistic model was built using clinical, ultrasonographic and endocrine parameters to predict the response to rFSH treatment, adjusted for the number of cycles performed. RESULTS: In total, 85 women underwent 272 treatment cycles with rFSH, of which 57 women (67%) achieved an ongoing pregnancy. Oligomenorrhoea, shorter duration of infertility and a lower free androgen index (FAI) were associated with higher chances of an ongoing pregnancy, resulting in a predictive model with a modest discriminative power (area under the curve 0.72, 95% confidence interval 0.64-0.79) that allowed us to distinguish between women with a probability of <5% of attaining an ongoing pregnancy and women with a probability of >25% of doing so. CONCLUSION: A model consisting of oligo/amenorrhoea, duration of infertility and FAI level allowed a distinction to be made between women with a poor chance and women with a good chance of achieving an ongoing pregnancy.

Adult↗
PubMed1996

Ovulation induction combined with intrauterine insemination in women 40 years of age and older: is it worthwhile?

The use of ovulation induction combined with intrauterine insemination (IUI) as a treatment for subfertility in women with patent Fallopian tubes has increased in recent years. Little is known regarding the efficacy of this treatment in women aged >/=40 years. We reviewed our data in our ovulation induction with IUI programme for 168 consecutive patients aged >/=40 years undergoing a total of 469 cycles of treatment. Either sequential clomiphene citrate and human menopausal gonadotrophins or daily gonadotrophins were utilized along with timed IUI insemination. In 402 completed cycles, 28 clinical pregnancies occurred. The pregnancy loss rate was 34.4%. The overall ongoing/viable pregnancy rates per initiated and completed cycles were 4.47 and 5.22% respectively. No viable pregnancies occurred in 136 cycles in women aged >/=43 years. The ongoing/variable cycle fecundity rates for women aged 40, 41, and 42 years were 9.6, 5.2, and 2.4% per cycle respectively. When utilized in women aged >=40 years, ovulation induction with IUI is most likely to result in successful pregnancy in women 40-42 years of age. Women >/=43 years should consider other alternatives such as adoption or egg donation.

Adult↗
PubMedDate not supplied

A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer.

BACKGROUND: Anovulation has been hypothesized to decrease the risk of breast cancer. Therefore, infertility attributed to ovulatory disorders and ovulation-induction therapy may influence breast cancer risk. METHODS: We analyzed prospectively collected data from the Nurses' Health Study II, a cohort of 116,671 female registered nurses aged 25 to 42 years at baseline. Information on infertility was assessed every 2 years starting in 1989, ovulation induction was assessed every 2 years from 1993 to 1997, and incident cases of breast cancer were included through 2001. RESULTS: During 1,275,566 person-years of follow-up (1989-2001), 1357 incident cases of invasive breast cancer were diagnosed. Overall, women who reported infertility due to ovulatory disorder had a significantly lower incidence of breast cancer than women who did not report problems conceiving during a 12-month period (covariate-adjusted hazard ratio, 0.75; 95% confidence interval, 0.59-0.96). The incidence of breast cancer was lowest among women with infertility due to ovulatory disorder who received ovulation-induction therapy (covariate-adjusted hazard ratio, 0.60; 95% confidence interval, 0.42-0.85). CONCLUSIONS: Among women who participated in the Nurses' Health Study II, we observed an inverse association between infertility due to ovulatory disorder and breast cancer incidence. We observed the greatest reduction in the incidence of breast cancer for women who reported ovulatory disorder and use of ovulation-induction therapy, but these results should be interpreted with caution because these women may be the most infertile.

Adult↗
PubMed1984

Sonographic depiction of endometrial changes occurring with ovulation induction.

Endometrial thickness and texture were evaluated with serial pelvic sonograms in ten normal, menstruating women and 107 patients undergoing ovulation induction for in vitro fertilization. Serial sonograms were performed in the control group every other day throughout the menstrual cycle, whereas the sonographic examinations of the ovulation induction patients were performed daily in a four- to eight-day time interval after their medications were completed and prior to laparoscopy for follicular aspiration. Endometrial thickness increased (defined as a persistent change greater than or equal to 1 mm) in 21 of 53 women (40 percent) who received human menopausal gonadotropin (HMG). Of the 54 women treated with clomiphene citrate (CC), five of 12 (42 percent) at 50 mg daily, 13 of 33 (39 percent) at 100 mg daily, and one of nine (11 percent) at 150 mg daily were found to have endometrial thickening. Although the frequencies of endometrial thickening in the high-dose CC and HMG groups were not significantly different (P = 0.09), the peak estradiol (E2) levels in the CC (150 mg) group (E2 = 944 +/- 165 pg/ml) were significantly higher (P less than 0.001) than those in the HMG group (E2 = 584 +/- 26 pg/ml). The relatively low frequency of endometrial thickening in women receiving CC (150 mg) despite very high E2 levels, and the decreased incidence of endometrial thickening relative to increasing dosages of CC may reflect an antiestrogenic effect of CC on the endometrium. In those patients undergoing ovulation induction, the texture of the endometrium remained the same in 98 cycles and changed during nine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗