Ovulation-inducing Drugs Research Articles

P-795: Effectiveness of using hMG-low dose hCG-GnRH antagonist protocol with unsuccessful hMG-GnRH antagonist protocol cases (full term pregnancies had not resulted) in-vitro fertilization (IVF) cycles

GnRH antagonist does not create flare-up effects such as are seen with GnRH agonist, and secretion of gonadotropin is immediately controllable. However, a decrease in the number or quality of oocytes extracted occurs as a result of the strong effects of GnRH antagonist in some cases. The purpose of our study was to consider what kind of results can be obtained by using hCG at 50 units from the day of GnRH antagonist use in cases that had not previously reached full term pregnancy using the hMG-GnRH antagonist protocol. Retrospective evaluation using the patient’s previous IVF stimulation attempts as a historical control. The subjects were 14 cases on whom IVF was carried out (28 cycles: 14 cycles with oral contraceptive pill-hMG-GnRH antagonist protocol and 14 cycles with oral contraceptive pill-hMG-low dose hCG-GnRH antagonist protocol). All the cases had been unsuccessful even though the antagonist protocol not using low dose hCG had been carried out (full term pregnancies had not resulted). Regarding the ovulation induction method, an oral contraceptive pill was used from day 3 of menstruation in the cycle prior to extracting the eggs. Ovarian stimulation was started from day 4 after completion of a course of oral contraceptive pills. In both antagonist protocols the type of ovulation induction drug was changed depending on the LH level just before beginning ovarian stimulation. When serum LH was more than 1.5mIU/ml, pure urinary FSH or recombinant FSH was used, and when serum LH was less than 1.5mIU/ml hMG (Humegon, Organon, Osaka) was used. Daily hypodermic injections of Cetrorelix 0.25 mg/day were started from the time the leading follicle reached 14 mm. The treatment regime was changed to hMG (Pergogreen:in a ratio of FSH and LH at one to one) from the day Cetrorelix was started. Urinary hCG at 50 units was used together with hMG from the day that use of Cetrorelix was started in the low dose hCG protocol. When the average diameter of the leading follicle reached 20 mm, the type of ovulation induction drug was changed to hCG at 10000 units. No statistical difference was noted between the two groups for the amount of hMG (no low dose hCG group 2680.4±1039.5 vs low dose hCG group 3235.7±1171.5). However, the mean number of oocytes retrieved was significantly higher in the low dose hCG group (no low dose hCG group 9.7±3.7 vs low dose hCG group 14.6±6.3, p<0.05). The fertilization rate was significantly higher in the low dose hCG group (no low dose hCG group 57.1% vs low dose hCG group 69.6%, p<0.05). The blastomere number on the day 3 was significantly higher in the low dose hCG group (no low dose hCG group 6.0±2.4 vs low dose hCG group 7.0±2.2, p<0.05). Moreover, the blastocyst formation rate was significantly higher in the low dose hCG group (no low dose hCG group 37.5% vs low dose hCG group 63.0%, p<0.05). No statistical difference was noted between the two groups for the clinical pregnancy rate (FHM) per ET (no low dose hCG group 7.7% vs low dose hCG group 33.3%). The results of this study suggest that increases in the number of oocytes extracted, the fertilization rate, the average number of day 3 blastomeres, and blastocyst formation rates can all be increased by using low dose hCG to control the overly strong effectiveness of GnRH antagonist in cases that had not reached full term pregnancy using the GnRH antagonist protocol.

Tamoxifen citrate for women with unexplained infertility.

To assess whether administration of tamoxifen citrate (TMX) to women with unexplained infertility is beneficial. The primary outcome was the clinical pregnancy rate. In a prospective randomized trial, 66 consecutive women with unexplained infertility were recruited for the study. Thirty-six women received TMX at a 20-mg dosage and 30 women received no ovulation-induction drugs. Fourteen patients in the TMX group stopped taking TMX, and observations were terminated because of antiestrogenic effects. The pregnancy rate (PR) per patient and the PR per cycle were significantly decreased (P < 0.005) in the TMX group than in the spontaneous group. Kaplan-Meier tests showed that the cumulative PR in the TMX group was significantly lower than in the spontaneous group (P < 0.05). Ten of 14 patients who had stopped taking TMX became pregnant in spontaneous cycles. Administration of tamoxifen to women with unexplained infertility is not efficacious in terms of increasing the clinical PR.

Infertility, Ovulation Induction Treatments and the Incidence of Breast Cancer—a Historical Prospective Cohort of Israeli Women

Ovulation induction drugs may be associated with increased breast cancer risk. Results so far have been inconclusive. To evaluate the association between infertility, exposure to ovulation induction drugs and the incidence of breast cancer. Historical prospective cohort and nested case-control study. Institutional practice About 5,788 women attending five infertility centers in Israel between 1964 and 1984. Abstracting of medical records and telephone interviews. Breast cancer incidence was determined through linkage with the National Cancer Registry database. Standardized incidence ratios (SIRs) and 95% confidence intervals were computed by comparing the observed to the expected cancer rates in the general population. In addition, a nested case-control study within the cohort was performed with interviews of breast cancer cases and two matched controls. The study cohort included 120,895 women years of follow-up. Compared to 115.2 expected breast cancer cases, 131 cases were observed (SIR = 1.1; 95% CI 0.9-1.4). Risk for breast cancer was significantly higher for women treated with clomiphene citrate (SIR = 1.4; 95% CI 1.0-1.8). Similar results were noted when comparisons were carried out between treated and untreated women, and when multivariate models were applied. In the nested case-control study, higher cycle index (OR = 2.2; 95% CI 1.0-4.8) and treatment with clomiphene citrate (OR=2.7; 95% CI 1.3-5.7) were associated with higher risk for breast cancer. Infertility and usage of infertility drugs in general are not associated with increased risk for breast cancer. However, for infertile women treated with clomiphene citrate, breast cancer risk is elevated.

LH in the follicular phase: neither too high nor too low

The role of LH in the natural menstrual cycle is not disputed. However, there are a variety of opinions regarding the potential role of exogenous LH in ovulation induction and whether it is actually needed. Recent years have seen renewed interest in this issue for several reasons. First, ovulation-inducing drugs are increasingly being administered to normally ovulating women. Second, recombinant human FSH products completely devoid of LH activity are now available. Third, gonadotrophin-releasing hormone (GnRH) analogues (agonists and antagonists) prevent the untimely LH surge but also suppress endogenous LH activity during the follicular phase. This review analyses whether or not all patients need LH for follicular growth stimulation and new opportunities for improved treatment as a result of the availability of recombinant human LH both in patients with ovulatory disorders (World Health Organization (WHO) groups I and II anovulatory patients) and those undergoing multiple follicular development for assisted reproduction.

Management of Multiple Pregnancy: Labor and Delivery

Over the past 20 years, the number and rate of multiple births have dramatically increased in the United States. The rise in multiple births is mainly attributable to the increased use of ovulation-inducing drugs and the newly developed assisted reproductive technologies such as in vitro fertilization. Multifetal gestation is associated with an increased risk of perinatal morbidity and mortality. Multiple births account for an increasing percentage of low-birth-weight infants, preterm births, and infant mortality. In this article, the management of the labor and delivery of multiple gestation are reviewed. Particular emphasis is placed on the mode of delivery of twin and triplet pregnancies. Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader should be able to describe the effects of the rising rate of multiple pregnancies on perinatal morbidity and mortality, to recall the complications of diagnosing and treating abnormalities of multiple pregnancies and to list the different safe options in managing labor in a multiple gestation.

Management of Multiple Pregnancy

Over the past 20 years, the number and rate of multiple births have dramatically increased in the United States. The rise in multiple births is mainly attributable to the increased use of ovulation-inducing drugs and the newly developed assisted reproductive technologies such as in vitro fertilization. Multifetal gestation is associated with an increased risk of perinatal morbidity and mortality. Multiple births account for an increasing percentage of low-birth-weight infants, preterm births, and infant mortality. In this article, the unique complications of multiple gestation and their management are reviewed. Also, selective termination and multifetal reduction in multiple gestation are discussed. Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader should be able to describe the effects of the rising rate of multiple pregnancies on perinatal morbidity and mortality, to recall the complications of diagnosing and treating abnormalities of multiple pregnancies, to list the multiple severe complications associated with multiple gestations, and to describe the difficulty in managing these complications.

Management of Multiple Pregnancy: Prenatal Care???Part I

Over the past 20 years, the number and rate of multiple births have dramatically increased in the United States. The rise in multiple births is mainly attributable to the increased use of ovulation-inducing drugs and the newly developed assisted reproductive technologies such as in vitro fertilization. Multifetal gestation is associated with an increased risk of perinatal morbidity and mortality. Multiple births account for an increasing percentage of low-birth-weight infants, preterm births, and infant mortality. In this section, we address the management of the multifetal pregnancy, focusing on the maternal physiology, the diagnosis, the pregnancy outcomes, and the antenatal management of multiple gestation. Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader should be able to describe the effects of the rising rate of multiple pregnancies on perinatal morbidity and mortality, to recall the complications of diagnosing and treating abnormalities of multiple pregnancies, and to list the many changes that occur in both the mother and the fetuses in multiple pregnancies.

Food fortification with folic acid and rate of multiple births, 1994–2000

Since fortification of cereal grain products with synthetic folic acid (FA) became mandatory in January 1998, women in the United States who have become pregnant have been exposed to a higher level of FA than women who became pregnant previously. Some studies have suggested that increased FA consumption might increase the risk of multiple gestation pregnancies. Women who had a live birth in Kaiser Foundation Health Plan hospitals from January 1, 1994 through December 31, 2000; all multiple births; and the use of ovulation-inducing drugs were ascertained from electronic databases. Medical records of a sample of women with multiple births who did not use ovulation-inducing drugs were reviewed to determine whether they used assisted reproductive technology. Exposure to FA-fortified foods was based on date of delivery. The rate of multiple births increased from 13.6 to 14.8 per 1000 live births from 1994 through 2000. The percentage of women who had a multiple birth and who filled a prescription for an ovulation-inducing drug in the 12 months before delivery increased from a low of 6.6% in 1994 to a high of 14.9% in 2000. After excluding women using ovulation-inducing drugs, the increased rate of multiple births was no longer observed. While the rates of multiple births have increased since FA fortification became mandatory, this increase can be explained by the increased use of ovulation-inducing drugs. Our findings show no relationship between food fortification with FA and the rates of multiple births in this large, managed health care population.

A Case-Control Study of Ovarian Cancer in Relation to Infertility and the Use of Ovulation-inducing Drugs

The authors conducted a population-based, case-control study among women aged 35-54 years to assess the influence of infertility and use of ovulation-inducing drugs on ovarian cancer risk. The study was conducted from 1994 to 1998 in three regions (metropolitan Atlanta, Georgia, Detroit, Michigan, and Seattle, Washington) and included 378 cases and 1,637 controls. Data were obtained through in-person interviews, and analysis was conducted using unconditional logistic regression. Among parous women, the authors observed no association of cancer risk with a history of infertility, medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Among nulliparous women, risk was increased among women with a history of infertility (odds ratio = 1.6, 95% confidence interval: 1.0, 2.6), particularly when infertility first became manifest relatively late in reproductive life (for first infertility at > or =30 years of age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.5); risk was not associated with medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Findings were similar when borderline and invasive epithelial tumors were considered separately. While the results of this study support the hypothesis that a subset of nulliparous women who experience infertility may be at increased risk of ovarian cancer, the reasons for this increase in risk remain unclear.

Association between fertility drugs and gynecologic cancers, breast cancer, and childhood cancers

Ovulation-inducing drugs have been widely used for various types of infertility since the beginning of 1960s and their use increases day by day parallel to the success achieved in fertility treatment. However, the researches performed in the last two decades have begun to discuss about the safety of these drugs and the risks associated with their use. Especially, the potential neoplastic effects of these drugs are increasingly questioned. The studies have discussed whether there is an association between the exposure to ovulation-inducing drugs and the incidence of various cancers. Moreover, several studies have been performed to reveal whether there is an increased risk of childhood cancers in children conceived after fertility treatment. The point we reached through the available data is that the risk of breast, uterine and invasive ovarian cancers is not increased, but the risk of borderline ovarian tumors might increase after such a therapy. The risk of cancer has been found similar for children conceived after fertility treatment and those conceived naturally. It should also be kept in mind that cancers are overdiagnosed in infertile women population because of the close medical surveillance, which may also contribute to the early detection of cancers. Although it is still early to state the last words on this topic, the possible association should be addressed when obtaining an informed consent before starting treatment.

Cancer Risk After the Use of Ovulation-Stimulating Drugs

This large retrospective study investigating the effect of ovulation-stimulating drugs on the subsequent risk of ovarian cancer included infertility patients from 5 large reproductive endocrinology centers in the years 1965 to 1988. Information was gathered from extensive review of medical records, follow-up data, patient questionnaires mailed in 1998 (10 years after the last year of inclusion), and cancer registries or similar sources such as the National Death Index. Clomiphene citrate (3277 patients) and human gonadotropins, including Pergonal (Serano, Rockland, MA), Humegon (Organon, West Orange, NJ), or Metrodin (Serono) (866 patients), were used for ovulation stimulation. The diagnoses of cancer were verified in discharge summaries and operative and pathology reports. The total number of infertility patients was 12,193. Figure 1 shows the procedure followed for data management. Over 80% of the patients had at least 15 years of follow up (median follow-up period 18.8 months). There were 45 cases of ovarian cancer diagnosed in the total number of infertility patients. Table 1 shows the risk of ovarian cancer in the study patients, with and without exposure to ovulation-inducing drugs, compared with the general population. The risk for infertility patients was 1.98 (95% confidence interval [CI], 1.4–2.6). There were no significant increases in the risk of ovarian cancer among patients who received either clomiphene or gonadotropins. There were also no significant differences in risk between patients who took clomiphene and those who took gonadotropins. Eleven women died from ovarian cancer (standardized mortality ratio [SMR], 1.94; 95% CI, 0.3–4.2). The rate of mortality did not differ between those who received ovulation-inducing drugs and those who did not. Extensive analysis of possible risk factors for ovarian cancer, including demographic data, causes of infertility, medical history, and histologic findings, with adjustment for infertility drug use, found only 1 significant predictive variable. Zero gravidity at the first clinic visit was the only factor with a significant influence on the development of ovarian cancer (42.3% of those without ovarian cancer compared with 57.8% of those who developed ovarian cancer; P <0.05). Use of clomiphene or gonadotrophins did not influence the development of ovarian cancer. There was also no effect seen when considering either total dosage or exposure to both clomiphene and gonadotropins. Except for zero gravidity, no subset of patients was seen that had an increased risk of ovarian cancer compared with the total study group.Fig. 1: Field and analytic status of eligible study subjects, women evaluated for infertility, 1965–1988. Reproduced with permission. Obstet Gynecol 2004;103:1194–1203. Copyright © 2004, Lippincott Williams & Wilkins. All rights reserved.TABLE 1: Standardized incidence ratios comparing ovarian cancer among infertile patients with the general population, overall and stratified by usage of clomiphene and gonadotropins

Infertility treatment with ovulation-inducing drugs exacerbates gingival inflammation, gingival crevicular fluid and oral bleeding

Infertility treatment with ovulation-inducing drugs exacerbates gingival inflammation, gingival crevicular fluid and oral bleeding

Association between fertility drugs and gynecologic cancers, breast cancer, and childhood cancers

Ovulation-inducing drugs have been widely used for various types of infertility since the beginning of 1960s and their use increases day by day parallel to the success achieved in fertility treatment. However, the researches performed in the last two decades have begun to discuss about the safety of these drugs and the risks associated with their use. Especially, the potential neoplastic effects of these drugs are increasingly questioned. The studies have discussed whether there is an association between the exposure to ovulation-inducing drugs and the incidence of various cancers. Moreover, several studies have been performed to reveal whether there is an increased risk of childhood cancers in children conceived after fertility treatment. The point we reached through the available data is that the risk of breast, uterine and invasive ovarian cancers is not increased, but the risk of borderline ovarian tumors might increase after such a therapy. The risk of cancer has been found similar for children conceived after fertility treatment and those conceived naturally. It should also be kept in mind that cancers are overdiagnosed in infertile women population because of the close medical surveillance, which may also contribute to the early detection of cancers. Although it is still early to state the last words on this topic, the possible association should be addressed when obtaining an informed consent before starting treatment.

Ovarian Cancer in a Woman Who Had Undergone Multiple Ovarian Stimulation Cycles and Its Subsequent Spread after Laparoscopic Surgery

Objective: To report on a woman with a history of multiple ovarian stimulation cycles using clomiphene citrate who developed ovarian cancer and its subsequent spread after laparoscopic surgery. Case Report(s): A 29-year-old woman suffered from secondary infertility. She failed to conceive after 6 consecutive cycles of clomiphene citrate. A laparoscopic operation was arranged due to a persistent echolucent cystic mass found during ovulation induction. This mass turned out to be a well-differentiated endometrioid adenocarcinoma. Subsequent exploratory laparotomy found cancer progression with implants at the trocar site and on the ovarian and peritoneum surface. Conclusion(s): Although a possible link between ovulation induction drugs and the risk of ovarian carcinoma is inconclusive, one should be very cautious when prescribing ovulation induction agents. Any persistent adnexal mass should be carefully evaluated. Immediate conversion to surgical staging is necessary once a malignancy is found during a laparoscopic examination.

A simple solution to reducing multiple pregnancy rates: utilizing age as the predominant factor

Background: According to the Educational Bulletin published by American Society for Reproductive Medicine, November 2000 issue, multiple pregnancies have increased over the past 15 years. 40% of these pregnancies were attributable to ovulation induction drugs without assisted reproductive technologies (ART), and 40% were attributable to ART. Objective: We reviewed our multiple gestation rates after the implementation of the policy of ≤2 embryos would be transferred in women <35 yr. in a fresh IVF cycle. In this age group with a previous history of failed IVF were assessed on a case-by-case basis and did not necessarily fall into this category. Materials and Methods: A retrospective analysis of multiple pregnancy rates for the years 2000 and 2001 was performed. ART cycles for 2000 and 2001 were included in the analysis and subgroup analysis was performed on IVF only (all and <35 years), as well as ART (all and <35 years). Statistical analysis was performed by chi-square analysis. Results: All triplet rates except for ART procedures performed on women <35, were significantly reduced without a negative impact on pregnancy rates and without performing selective fetal reductions in the year 2001. Conclusion: Since the implementation of this policy, this clinic has experienced a significant reduction in multiple pregnancies. The results of this retrospective analysis suggest the possibility that this policy of limiting the number of embryos transferred in young women could also be extended to other types of ART cycles. Based on these results, we have implemented this policy in our frozen embryo transfer (FET) and donor egg cycles without jeopardizing our pregnancy rates. Table 1 Table 1Ongoing pregnancy rates for 2000 & 2001.GroupsSingletonsTwinsTriplets∗P values (Power)2000 (%)2001 (%)2000 (%)2001 (%)2000 (%)2001 (%)ART257/420 (61.2)259/387 (66.9)137/420 (32.6)118/387 (30.5)26/420 (6.2)∗10/387 (2.6)∗0.021 (0.635)ART (<35)137/232 (59.1)133/206 (64.6)80/232 (34.5)67/206 (32.5)15/232 (7.8)6/206 (2.9)IVF186/327 (56.9)186/289 (64.4)116/327 (35.5)95/289 (32.9)25/327 (7.6)∗8/289 (2.8)∗0.012 (0.713)IVF (<35)105/193 (54.4)109/170 (64.1)73/193 (37.8)57/170 (33.5)15/193 (7.8)∗4/170 (2.4)∗0.038 (0.538) Open table in a new tab

Patients chose Gonal-F multidose more often than follistim or Gonal-F ampules because of perceived physician recommendation

Objective: To identify factors influencing patient medication selection for both follicle stimulation and ovulation induction drugs when all drugs are presented and the patient may chose which drugs to use.

Are fertility drugs a risk factor for persistent trophoblastic tumour?

The introduction of ovulation-inducing drugs has raised concern that women exposed to these therapies may be at increased risk of cancer. We assessed the potential association between exposure to fertility drugs and the risk of developing persistent trophoblastic tumour (PTT). We conducted a systematic review of the English and non-English language literature using the National Library of Medicine's Medline to identify all observations of patients with hydatidiform mole (HM) after treatment with ovulation-inducers. Fifty-two cases were considered including 26 singleton molar pregnancies and 26 multiple molar pregnancies consisting of an HM and one or more co-existent fetus(es) (HM-and-CF). PTT occurred in 15% of patients with singleton HM and in 42% of patients with HM-and-CF, 15% of whom had a metastatic disease. Of those patients with HM-and-CF, 16 patients delivered at <24 weeks gestation, mostly because of vaginal haemorrhage. Ten patients delivered at > or = 24 weeks of gestation, six of whom (25%) had a normal live child. These results are similar to spontaneously conceived pregnancies. Although women having an HM after therapy with ovulation-inducing drugs seem to have no added risk of PTT, multiple pregnancies are more likely to occur, and the overall risk may be increased.

IUD use and the risk of endometrial cancer

Objective: Although the intrauterine device (IUD) is one of the most widely used forms of contraception throughout the world, its potential long-term effects on the uterus have not been thoroughly evaluated. This paper reports the long-term results of IUD use on the incidence of endometrial cancer. Study design: The data is part of a nationwide case-control, pilot study that was undertaken in order to evaluate the possible influence of ovulation induction drugs on the risk of endometrial cancer. The study included 128 living women 35–64 years old, with a histologically confirmed diagnosis of endometrial carcinoma. The controls were 255 women from the same dialing areas selected by random digit dialing. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. Results: The following parameters were found to be independently associated with endometrial cancer controlling for age: nulliparity OR=2.7 (95% CI 1.1–6.5, P=0.03); history of infertility OR=1.8 (95% CI 1.0–3.3, P=0.05); BMI≥27 OR=2.3 (95% CI 1.4–3.8, P=0.001). The use of oral contraceptives and IUD were found to be protective; OR=0.29 and 0.37, respectively, (95% CI 0.14–0.61, P=0.001, 0.19–0.70, and 0.003, respectively). Conclusions: IUD use may have a protective effect on endometrial cancer risk. The protective effect of IUD may be either, through the intense inflammatory response that leads to other lisosomal and inflammatory actions, which may include cells responsible for early elimination of hyperplastic endometrial epithelial cells or, the more complete shedding of the endometrium associated with IUD use may decrease hyperplasia of the endometrium, a known risk factor for endometrial carcinoma.

Preeclampsia in Multiple Gestation

In Brief OBJECTIVE To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. METHODS This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. RESULTS Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P < .05 level. CONCLUSION Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously. Adjusted for maternal age and parity, there is a 2.1-fold increased risk of preeclampsia among women conceiving multiple gestations through assisted reproductive technologies compared with spontaneously-conceived multiple gestations.

Preeclampsia in multiple gestation: the role of assisted reproductive technologies.

To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.