Using infertile patients in epidemiologic studies on subfecundity and embryonal loss

Abstract

Subfecundity is a frequent and serious problem that may sometimes be preventable, but we need to know more about its determinants. Different epidemiologic designs are available. The best of these use prospectively collected data from the population, but they are time consuming, expensive and often hampered by low-participation rates. Most patients undergoing infertility treatment are closely monitored for clinical reasons, making it feasible to use secondary data to study the period from conception to implantation and pregnancy. In spite that infertility patients are highly selected, there are specific exposure-effect relations that can be studied in cohorts of infertility patients. These patients offer a potentially useful setting for studying exposures that operate late in fertilization, whereas the designs may be inadequate to identify exposures that cause reduced sperm counts, anovulation and total occlusion. The clinical sampling and the treatment set limitations for what can be studied. In certain situations, infertile patients can, however, provide useful epidemiologic evidence for learning about the causes of subfecundity.

Female Infertility and “Emerging” Organic Pollutants of Concern

“…Populations using assisted reproductive technologies (ART), including IVF, tend to be Bhighly selected,^com-prised of couples who intensely desire but are unable to have a child, seek medical attention for infertility, and have exhausted conventional treatments [63,64]. If social and economic factors governing ART usage, such as higher income, are also associated with exposure to EOPs, generalizability may be limited [63,65]. For example, greater wealth was associated with higher urine BP-3 levels and lower urine MBP and MiBP levels in U.S. biomonitoring studies [66].…”

“…For example, greater wealth was associated with higher urine BP-3 levels and lower urine MBP and MiBP levels in U.S. biomonitoring studies [66]. Still, general population recruitment poses significant challenges, given that <1-2 % of reproductive aged couples reported to be planning near future pregnancies [67][68][69], and high participant study burdens appear to be better tolerated by reproductive health clinic populations [65]. -We considered prospective capture of time to pregnancy (TTP), the number of menstrual cycles with unprotected heterosexual intercourse prior to a pregnancy, coupled to hCG testing on the day of expected menses, as ideal for outcome assessment.…”

“…Exposure misclassification is possible given the short half-life of BPA, yet it was likely modest given that two specimens were averaged for most cycles. Furthermore, an infertile reference group precluded the introduction of selection bias, likely if comparing clinic to non-clinic populations [65]. However, this also may limit generalizability of study results, as women conceiving spontaneously may have different characteristics leading to exposure [63,64].…”

“…In addition, no adjustments were made for confounders, although PREVIENI reported similar age and BMI in the groups. Importantly, women receiving infertility treatment may be dissimilar to the general population in terms of behavior influencing exposure [63,64], and medical therapy may itself inflate exposure [30], and so, a clinic-based comparison group is preferable [65]. An additional concern comes from the use of serum biomarkers to determine primary phthalate monoesters and BPA, which was criticized due to a possibility for extraneous introduction of parent compounds into the specimen during collection, with subsequent in situ metabolism by endogenous hydrolases, and so urine preferred [91].…”

Maternal Recognition of Pregnancy

“…The infertility clinic case-control studies tend to emphasize pregnancy success and not the etiology of the infertility. 18 Tielemans et al, 19 utilized a case-control study of infertility patients to show an association between aromatic solvents and abnormal semen quality. Study subjects were in four groups: normal semen analysis (controls), those with a semen value below the World Health Organization (WHO) reference value, those with very poor semen quality (sperm concentration < 5 million, percent motile < 10%, or normal morphology < 5%), and azoospermic men.…”