Infertility Medications Research Articles

Infertility as a Cancer Risk Factor – A Review

Ovarian, endometrial and breast cancers are associated with several risk factors, such as low parity, infertility, early age at menarche, and late age at menopause. Frequently most of these risk factors coexist in infertile patients and some studies suggested that the different infertility causes can be involved in cancer risk development. In particular case–control and cohort studies investigated the possible role of ovulatory disorders, endometriosis and unexplained infertility in increasing the risk of this disease. Most studies have shown no overall increased risk in invasive ovarian cancer in subfertile patients, although nulliparity has been consistently associated with increased rates of ovarian tumor, in particular with borderline and endometrioid cancers in patients with a history of endometriosis. Different studies reported that infertile women are not at risk for breast cancer. However, women affected by infertility may be more at risk for endometrial cancer, particularly if affected by ovulatory disorders. Moreover, infertility is now often treated with medical devices that could by themselves modify the hormonal environment and be cofactors in the cellular changes towards cancer development. However, although early studies suggested that infertility medications were associated to increased risk in ovarian cancer, subsequent studies have been mainly reassuring, although suggesting that type and duration of medical treatment can increase the malignancy risk. An increased risk of endometrial cancer in patients undergoing infertility treatment has been reported, as expected by the similar structure shared by clomiphene and tamoxiphene. Since breast cancer is widely recognized as having a hormonal etiology, a possible role of fertility medications to promote cancer has been hypothesized. However, many large studies were not able to find an associated risk of breast cancer. In conclusion, nowadays, firm answers about the precise effects of infertility and its treatment on cancer risk are not available but findings are generally reassuring. Further studies about fertility drug treatments on larger populations may offer in the future longer follow-up and more precise data with better adjustments for confounding factors.

Strategies for designing an efficient insurance fertility benefit: a 21st century approach

Creating a 21st century insurance benefit for infertility should be cost effective. Savings can be realized by eliminating hidden infertility costs, eliminating payments for ineffective treatments, and providing coverage for effective 21st century treatments, thus reducing costs associated with iatrogenic multiple pregnancies. The new benefit allows patients to attempt 21st century forms of infertility treatments while being managed by certified infertility providers. Industry and insurance carriers might save money by examination and implementation of this concept.

Empty follicle syndrome in the setting of dramatic weight loss after bariatric surgery: case report and review of available literature

To describe empty follicle syndrome, potentially due to route of human chorionic gonadotropin (hCG) administration, in a patient who had previously undergone bariatric surgery. Case report and review of literature. Academic medical center. A 42-year-old nulliparous, morbidly obese woman who had presented for assisted reproduction treatment after having lost 175 pounds via gastric bypass surgery, resulting in abdominal skin redundancy. The patient's gastric bypass surgery had resulted in abdominal skin redundancy. In her first cycle, recombinant hCG was used with a luteal gonadotropin-releasing hormone (GnRH) agonist/recombinant follicle-stimulation hormone (FSH) protocol. At hCG administration, her estradiol level was 2342 pg/mL, and 18 follicles were measured. At retrieval, no oocytes were recovered, and her serum hCG level was 19 mIU/mL. In the subsequent cycle, identical ovarian stimulation was performed, with peak estradiol of 2891 pg/mL, but intramuscular hCG was administered. At retrieval, her serum hCG level was 45 mIU/mL, and 19 oocytes were recovered, resulting in 10 embryos. Five embryos were transferred, and a singleton pregnancy resulted. Recovery of oocytes. Clinical pregnancy. Abdominal skin redundancy after bariatric surgery may alter the absorption of subcutaneously administered infertility medications. Additional studies are needed to treat infertile patients optimally after weight-reduction surgery.

The Effect of Infertility Medication on Thyroid Function in Hypothyroid Women Who Conceive

To determine whether infertility medications alter thyroid status in patients with treated hypothyroidism, and whether resulting pregnancies require additional thyroid supplementation compared with those conceived spontaneously. Prospective observational study of 18 infertility patients with treated hypothyroidism who conceived between July 2005 and July 2006 with or without infertility medications. Thyroid studies were performed prior to conception, at the time of pregnancy diagnosis, and approximately 6 weeks after an increase in thyroid replacement dose. Orally medicated conceptions were similar to spontaneous conceptions on all thyroid related variables, and therefore the two groups were combined for analysis. Although there was a nonsignificant difference in thyrotropin (TSH) levels postconception (3.8 mIU/L vs. 2.2 mIU/L, p = 0.30), there was no difference in TSH levels after increase in thyroid replacement dose (1.7 mIU/L vs. 1.1 mIU/L, p = 0.30) between patients who conceived after gonadotropin stimulation compared with those who conceived spontaneously or with oral medications. The mean percent dose increases for the nongonadotropin and gonadotropin pregnancy groups were 30.6% and 32.4%, respectively. Hypothyroid patients who conceive after gonadotropin stimulation or with oral medications for ovulation induction do not need additional thyroid supplementation compared with those who conceive spontaneously.

A Population-Based Study of Maternal and Perinatal Outcomes Associated with Assisted Reproductive Technology in Massachusetts

To assess associations between assisted reproductive technology (ART) and adverse maternal and infant outcomes, with an emphasis on singletons. We linked data from the US ART surveillance system with Massachusetts live birth-infant death records data for resident births in 1997-1998 and compared births conceived with ART (N = 3316) with births not conceived with ART or infertility medications (N = 157,066) on: maternal chronic conditions, pregnancy complications, labor and delivery complications, and perinatal and infant outcomes. Overall, ART was strongly associated with numerous adverse outcomes. The magnitude was reduced for several outcomes when analyses were limited to singletons. After further exclusion of maternal subsets with rare ART births (maternal age <20; education <high school; unmarried, no or public health insurance; no or third trimester prenatal care initiation), and matching ART and non-ART singletons on birth hospital, birth month and year, maternal age, parity, and race/ethnicity, ART remained associated with pre-existing diabetes (Relative Risk [RR] = 2.2 95% confidence interval 1.02-4.9), incompetent cervix (RR = 6.0, [2.3-15.4]), pregnancy-induced hypertension (RR = 1.5, [1.04-2.2]), uterine bleeding (RR = 3.2, [1.5-6.8]), placental abruption (RR = 3.8 [1.6-9.4]), placenta previa (RR = 3.8, [1.6-9.4]), preterm delivery (RR = 2.4, [1.8-3.0]), very preterm delivery (RR = 2.5, [1.2-5.2]), low birth weight (RR = 2.1, [1.5-2.9]), and infant not discharged home (RR = 1.8, [1.2-2.6]). Women who conceive with ART are more likely than women who do not to enter pregnancy with a chronic condition and develop complications during pregnancy and labor and delivery. Additionally, infants born after ART are at increased risk for adverse health outcomes. The mechanisms underlying these associations require further study.

Potential association between infertility and spinal neural tube defects in offspring

We examined the possible association between infertility and spinal neural tube defects (NTDs). This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California. Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8). This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants.

Assisted reproductive technology and the incidence of ovarian cancer: a meta-analysis.

To systematically evaluate the available literature regarding the relationship between assisted reproductive technology and ovarian cancer. Computerized search of 6 databases from 1966 (or closest) to present: Cochrane Controlled Trials Register, Cancerlit, CINHAL, Current Contents, PubMed in process (formerly called PreMEDLINE), and MEDLINE. We collected references from the bibliographies of reviews, original research articles, content experts, and conference proceedings to find published and unpublished literature. Case-control and cohort studies are included. The population of interest is treated infertile women, the control population is untreated infertile women, and the intervention or exposure of interest includes the following fertility medications: clomiphene citrate, gonadotropins, human chorionic gonadotropin, and gonadotropin releasing hormone agonists. The primary outcome is incident, primary ovarian cancer. Three cohort and 7 case-control studies were included in the quantitative analyses. The Newcastle-Ottawa Quality Assessment Scales were used. Two investigators independently extracted study methods, sources of bias, and outcomes. The following information was recorded: publication information, subject characteristics, intervention information and outcomes. Studies combined were sufficiently homogeneous for quantitative summary. Case-control and cohort data showed a significantly elevated risk for exposure of infertility medications and ovarian cancer in subjects who underwent assisted reproductive technology compared with general population controls (1.52; 95% confidence interval [CI] 1.18 to 1.97). When cases of ovarian cancer were compared with infertile controls for exposure to infertility medications, the odds ratio (0.99; 95% CI 0.67, 1.45) was not elevated. However, cohort data comparing outcome in treated infertile patients with untreated infertile patients suggests that treated patients may tend to a lower incidence of ovarian cancer-odds ratio = 0.67 (95% CI 0.32, 1.41). Ovarian cancer does not appear to be increased in treated infertile patients versus untreated infertile patients. Treated infertile patients may have a lower incidence of ovarian cancer than untreated infertile patients.

Is there a true difference in the amount of drug delivered using different brands of 1 ml syringes versus the pen-injector device?

Objective: An area of prominent concern for nurses is teaching patients to inject their medications in a precise manner to insure they receive the full dose of the prescribed drug. Both technique and injection device are critical elements in this process, as the vast majority of infertility medications are administered by injection. In late 2001, a new device for drug administration, the Puregon Pen(r) (a pen-injector), was introduced in the Canadian market. An earlier report from the sponsor suggested that the actual amount of rFSH injected with a standard syringe was 18% less than anticipated when compared to the pen-injector(1). Based on this study the pen-injector is characterized as a precision device which delivers an exact dose and therefore, on average, delivers 18% more FSH per injection than a conventional syringe. Considering an average 10-day ART protocol using 225 IU/day, 2250 IU would be injected in total. According to the 18% waste presumption, 405 IU would not be delivered if syringes are used. This difference equates to more than 1.5 missed doses, which could negatively impact treatment outcome. Therefore, if the wastage claim is true, most patients have been under-dosed and have paid for more drug than they received. The objective of this study is to test the theory that the syringes are 18% less precise than the pen-injector for drug delivery.

Infertility medications and the risk of breast cancer

Every year is a big year, and a bad year, for breast cancer. Not surprisingly, many are interested in identifying risk factors for breast cancer, especially those that are potentially modifiable. Readers of Fertility and Sterility are no exception. In this issue, Burkman and colleagues report on a significant study of 4,575 breast cancer patients and examine whether use of drug therapies for infertility is associated with an increased breast cancer risk.

Response to: “Examining if infertility medications increase breast cancer risk”

Healy and Venn summarize in their critique the strengths and weaknesses of our study. Our major finding was that women using infertility drugs overall had no increased risk of breast cancer. However, women using human menopausal gonadotropin (hMG) for 6 months or for at least six cycles had an increased risk of breast cancer of between two and three times greater than that of other women. Although there are potential mechanistic or pathophysiologic explanations for this latter finding, none can be considered overly persuasive based on our current understanding of the mechanism of action of hMG.

Hormone and fertility drug use and the risk of neuroblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group.

Previous epidemiologic studies have suggested an association between maternal sex hormone use during pregnancy, including infertility medication, and an increased risk of neuroblastoma in the offspring. The authors conducted a case-control interview study from 1992 to 1996 that included 504 children less than 19 years of age whose newly diagnosed neuroblastoma was identified by two national collaborative clinical trials groups in the United States and Canada, the Children's Cancer Group and the Pediatric Oncology Group. Controls, matched to cases on age, were identified by random digit dialing. No association was found for use of oral contraceptives before or during pregnancy (first trimester odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.5, 2.1). The odds ratio was slightly elevated for history of infertility (OR = 1.4, 95% CI: 0.9, 2.1) and ever use of any infertility medication (OR = 1.2, 95% CI: 0.7, 2.2). Specifically, ever use of clomiphene was associated with a 1.6-fold increased risk (95% CI: 0.8, 3.0) but not periconceptionally or during the index pregnancy. A suggestive pattern was found for gender of the offspring, with an increased risk for males but not for females after exposure to oral contraceptives or clomiphene. This study did not find consistent and large increased risks for maternal use of hormones, but the suggestion of an association for male offspring requires further consideration.

Feminist critiques of new fertility technologies: implications for social policy.

This essay aims to show how feminist theoretical and practical perspective have enriched and deepened debate about moral and social issues generated by the proliferation and commodification of new reproductive techniques. It evaluates alternative feminist appraisals beginning with the first group to organize a collective response to the medicalization of infertility and explores several weaknesses working within their assessment: objectification of infertile women, naturalizing constructions of motherhood, hostility to technology, and an overly simplistic conception of power relations. Next, it shows how subsequent feminists have reframed the issues to overcome these weaknesses, drawing on themes prominent in recent theoretical debates: the need to reclaim women's agency, to revalue mothering, and to reappraise power relations. Lastly, it weighs the prospects for a collaborative politics that is sensitive to the social marginalization of vulnerable women and suggests practical strategies for responding to mounting pressures to procreate at any price.