Jansen, R. P. (1995). Elusive fertility: fecundability and assisted conception in perspective. Fertility and sterility, 64(2), 252-254. https://doi.org/10.1016/s0015-0282(16)57718-8
Jansen RP. Elusive fertility: fecundability and assisted conception in perspective. Fertil Steril. 1995;64(2):252-254. doi:10.1016/s0015-0282(16)57718-8
Jansen, Robert P.S. "Elusive fertility: fecundability and assisted conception in perspective." Fertility and sterility, vol. 64, no. 2, 1995, pp. 252-254.
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The last decade has transformed the physician's approach to infertility. The development of IVF for its treatment has so improved our capacity to overcome this most distressing of disabilities that we now need to revise many of our working ideas on how it can come about. This is not because new causes have been discovered. Rather, an appreciation has been gained of how apparently minor disturbances can combine to cause a major disruption in the expectation of pregnancy. At the best of times-and sometimes, no doubt, at the worst of times getting pregnant is a matter of chance. The parameter that describes this chance is the monthly probability of conception, known among epidemiologists as fecundability (f) (probability of achieving pregnancy in one menstrual cycle), and is similar to "monthly fecundity" (monthly probability of a live birth in one cycle exposed to the risk of pregnancy) (1). Like every statistic in biology, fecundability has a wide distribution of values in the population (modeled in Fig. 1). Figure 1 also illustrates a group of couples with a fecundability value of zero-meaning complete infertility, or sterility, which affects perhaps 5% of couples attempting to achieve a pregnancy.
An examination was made of the possibility that 100 to 200 ml of intraperitoneal 32% dextran 70 and/or 0.5% hydrocortisone sodium succinate (randomized independently with similar volumes of Ringer's lactate solution) might help to lessen the postoperative formation of adhesions among patients undergoing surgical procedures for peritubal adhesions (n = 76), endometriosis (n = 27), or midtubal occlusion (n = 61). Patients in the first two groups who were given intraperitoneal corticosteroids were also given systemic steroids. Nonparametric comparison of median adhesion scores at operation and at subsequent laparoscopy showed that there was a poorer outcome with dextran than when dextran was not used in every subgroup except one (repeat salpingolysis after previous operation for adhesions), including first operations for adnexal adhesions (Mann-Whitney U = 200, m = 23, n = 26; p less than 0.05). The probability was small (p beta less than 0.002) that an important beneficial effect of dextran was overlooked. Systemic corticosteroids were associated with a consistent trend toward improved outcome, especially in patients who initially had few or no adhesions, such as those operated on for endometriosis (U = 2, m = 7, n = 4; p less than 0.025), but among patients with tubal resections and anastomoses with adnexal adhesions the use of intraperitoneal hydrocortisone alone was associated with a worse outcome (U = 15, m = 12, n = 8; p less than 0.02). Life-table analysis of the accumulating probability of pregnancy showed that no significant difference resulted from adjunct use in any group. The conclusion is that no empiric basis supports the use of intraperitoneal 32% dextran 70 or 0.5% hydrocortisone in the attempt to prevent peritoneal adhesions, but further investigations on the systemic administration of corticosteroids to decrease the formation of adhesions would be useful.
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Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
To model the cumulative probability of pregnancy among couples with subfertility without a definitive diagnosis, according to different treatment strategies. A beta distribution of fecundity was fitted that reproduced the cumulative probability of pregnancy in prospective studies of natural fertility, and this distribution was applied to simulated cohorts starting with one million couples each. Probabilities of pregnancy were generated for each cycle of each couple. Simulation study. PATIENT(S): Hypothetic subfertile population. INTERVENTION(S): After 2 or 4 years of attempting pregnancy and diagnostic evaluation to exclude anovulation, tubal obstruction, and severe male factor, simulated treatments were applied to the remaining nonpregnant couples, with treatment effects based on published literature. MAIN OUTCOME MEASURE(S): Simulated cumulative probability of pregnancy. RESULT(S): Initially, the cumulative probability of pregnancy was highest for early treatment with IVF, but over time, conservative treatment or frequent intercourse approached the same cumulative probability. CONCLUSION(S): In couples without clear indications for IVF, the main benefit of early IVF may be to shorten time to pregnancy, a benefit that must be weighed against costs and potential adverse outcomes. Couples should be encouraged to maintain regular intercourse to maximize chances of pregnancy, even after unsuccessful treatment attempts.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Ecochard R, 2005·Revue d'epidemiologie et de sante publique
Heterogeneity in women and men's fecundity is a well-established fact. The selection process of men and women treated for infertility might bias the success rates of reproductive technology. Bias may also arise from frequency and timing of intercourse with respect to the day of ovulation. Several datasets were collected and analysed. They concern normally fertile couples who used natural family planning methods and infertile couples treated by artificial insemination with husband or donor's spermatozoa. The effects of heterogeneity on the success rates of treatment cycles are described and solutions are proposed as to data collection and statistical analysis in this specific field. The decrease in the success rates along successive cycles of assisted reproduction is a consequence of heterogeneity. The probability of conception varies among women and among men. After a first success, the probability of another success is higher. After a failure, the probability of success is lower. The most specialised centres treat the less fecund couples. There is a negative correlation between men and women's fertility in case of oligo/azoospermia. The fecund window cannot be correctly located by calendar calculations, but more appropriately by assessment of cervical mucus at the vulva. The variability of this location is wide. The decrease in the success rate with men and women's age results from a complex mixture of an increase in the proportion of sterile patients and a decrease in fecund patients' fecundity. Care should be taken to limit the bias due to patient selection and specific statistical methods should be used to allow for the progressive selection of patients during fertility studies and for the variability of the frequency and the timing of intercourse or insemination relative to ovulation.
Wise LA et al., 2023·Fertil Steril·Free full text on PubMed Central
To assess the effect of randomization to FertilityFriend.com, a mobile computing fertility-tracking app, on fecundability.
Parallel non-blinded randomized controlled trial nested within the Pregnancy Study Online (PRESTO), a North American preconception cohort. PATIENT(S): Female participants aged 21 to 45 years attempting conception for ≤6 menstrual cycles at enrolment (2013-2019). Randomization (1:1) of 5532 participants to receive a premium Fertility Friend (FF) subscription. MAIN OUTCOME MEASURE(S): Fecundability (per-cycle probability of conception). Participants completed bimonthly follow-up questionnaires until pregnancy or a censoring event, whichever came first. We first performed an intent-to-treat analysis of the effect of FF randomization on fecundability. In secondary analyses, we used a per-protocol approach that accounted for adherence in each trial arm. In both analyses, we used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those randomized vs. not randomized and applied inverse probability weights to account for loss-to-follow-up (intent-to-treat and per-protocol analyses) and adherence (per-protocol analyses only). Using life-table methods, 64% of the 2775 participants randomized to FF and 63% of the 2767 participants not randomized to FF conceived during 12 cycles; these respective percentages were each 70% among those with 0-1 cycles of attempt time at enrolment. Of those randomized to FF, 72% were defined as adherent (68% of observed menstrual cycles). In intent-to-treat analyses, there was no appreciable association overall (FR = 0.97; 95% CI, 0.90-1.04) or within strata of pregnancy attempt time at enrolment, age, education, or other characteristics. In per-protocol analyses, we observed little association overall (FR = 1.06; 95% CI, 0.99-1.14), but weak-to-moderate positive associations among participants who had longer attempt times at enrolment (FR = 1.15; 95% CI, 0.98-1.35 for 3-4 cycles; FR = 1.14; 95% CI, 0.87-1.48 for 5-6 cycles), were aged <25 years (FR = 1.29; 95% CI, 1.01-1.66), had ≤12 years of education (FR = 1.32; 95% CI, 0.92-1.89), or were non-users of hormonal contraception within 3 months before enrolment (FR = 1.10; 95% CI, 1.02-1.19). No appreciable associations were observed in intent-to-treat analyses. In secondary per-protocol analyses that accounted for adherence, randomization to FF was associated with slightly greater fecundability among selected subgroups of participants; however, these results are susceptible to unmeasured confounding.
DeVilbiss EA et al., 2020·Paediatr Perinat Epidemiol·Free full text on PubMed Central
Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability. To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles. We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy. After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; every other day or daily: 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, every other day: 88.8%; daily: 91.6%). In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.
Assisted Reproduction › Outcomes and Effectiveness › Cumulative Versus Per Cycle Reporting · Infertility › Evaluation › Prevalence and Incidence
PMID 7615098 7615098 DOI 10.1016/s0015-0282(16)57718-8 10.1016/s0015-0282(16)57718-8 Jansen et al. 1995, Jansen 1995
Cite this article
Jansen, R. P. (1995). Elusive fertility: fecundability and assisted conception in perspective. Fertility and sterility, 64(2), 252-254. https://doi.org/10.1016/s0015-0282(16)57718-8
Jansen RP. Elusive fertility: fecundability and assisted conception in perspective. Fertil Steril. 1995;64(2):252-254. doi:10.1016/s0015-0282(16)57718-8
Jansen, Robert P.S. "Elusive fertility: fecundability and assisted conception in perspective." Fertility and sterility, vol. 64, no. 2, 1995, pp. 252-254.
Keywords
Female, Fertility, Fertilization in Vitro, Humans, Infertility/therapy, Pregnancy
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