Reproductive Factors

Publications under ‘Reproductive Factors’ examine the association of characteristics, interventions and awareness of sexual and reproductive health with fertility and reproductive outcomes. 

Wise LA, Mikkelsen EM, Rothman KJ, Riis AH, Sørensen HT, Huybrechts KF, Hatch EE. A prospective cohort study of menstrual characteristics and time to pregnancy. Am J Epidemiol 2011; 174(6): 701-9.

Among Danish pregnancy planners, shorter menstrual cycle length was associated with longer time to pregnancy. Other menstrual factors, including age at menarche (first menstrual period), how long it took for menstrual cycles to become regular after the first menstrual period, and duration or intensity of menstrual flow, were not associated with fecundability.

Hahn KA, Wise LA, Riis AH, Mikkelsen EM, Rothman KJ, Banholzer K, Hatch EE. Correlates of menstrual cycle characteristics among nulliparous Danish women. Clin Epidemiol 2013; 5: 311-9.

We studied factors correlated with menstrual cycle characteristics among Danish women aged 18-40 who had never given birth. Women with low physical activity and heavy alcohol consumption were more likely to have irregular periods. High BMI, smoking, and caffeine and alcohol consumption were related to short menstrual cycles and heavy menstrual bleeding. Women in their mid-to-late thirties had shorter and lighter menstrual flow, but a lower prevalence of irregular cycles, compared with women age 18-25 years.

Mikkelsen EM, Riis AH, Wise LA, Hatch EE, Rothman KJ, Sørensen HT. Pre-gravid oral contraceptive use and time to pregnancy: a Danish prospective cohort study. Hum Reprod 2013; 28(5): 1398-405.

Among Danish pregnancy planners, women who used oral contraceptives (birth control pill) as their most recent form of birth control had a short-term delay (~3 menstrual cycles) in return of fertility. Long-term oral contraceptive use was associated with slightly increased fecundability.

Rothman KJ, Wise LA, Sørensen HT, Riis AH, Mikkelsen EM, Hatch EE. Volitional determinants and age-related decline in fecundability: a general population prospective cohort study in Denmark. Fertil Steril 2013; 99(7): 1958-64.

In the study of Danish pregnancy planners, we observed that fecundability of women is relatively stable with age until decreasing during age 35-40. Men also experience a small reduction in fecundability after age 35. Couples who had intercourse at least twice per week, used non-hormonal birth control (vs. hormonal birth control) before trying to conceive, and had intercourse during the fertile window had higher fecundability. However, these behaviors did not fully offset the decline of fecundability with age.

Hahn KA, Hatch EE, Rothman KJ, Mikkelsen EM, Brogly SB, Sørensen HT, Riis AH, Wise LA. History of oral contraceptive use and risk of spontaneous abortion. Ann Epidemiol 2015; 25(12): 936-941.

Among Danish pregnancy planners, oral contraceptive (birth control pill) use before becoming pregnant was not associated with risk of pregnancy loss before 22 weeks.

Hatch EE, Hahn KA, Mikkelsen EM, Riis AH, Sørensen HT, Rothman KJ, Wise LA. Pre-gravid oral contraceptive use in relation to birth weight: a prospective cohort study. Eur J Epidemiol 2015; 30(11): 1199-208.

Among Danish pregnancy planners, pre-pregnancy oral contraceptive (birth control pill) use within 6 months of conception was associated with a small increase in birth weight. However, long-term oral contraceptive use was associated with a small decrease in birth weight.

Wise LA, Mikkelsen EM, Sørensen HT, Rothman KJ, Hahn KA, Riis AH, Hatch EE. Prospective study of time to pregnancy and adverse birth outcomes. Fertil Steril 2015; 103(4): 1065-73.e2.

Among Danish pregnancy planners, women who took longer than 12 cycles to conceive had higher risk of several adverse birth outcomes, including preterm birth, low birthweight, placental disorders, and postpartum hemorrhage, after accounting for fertility treatment. Delayed conception was not associated with risk of small for gestational age birth (low birthweight compared to other infants born at the same gestational age).

Radin RG, Mikkelsen EM, Rothman KJ, Hatch EE, Sørensen HT, Riis AH, Kuohung W, Wise LA. Cesarean delivery and subsequent fecundability. Epidemiology 2016; 27(6): 889-93.

Among women who had previously given birth to 1 child, those who gave birth via Cesarean delivery with breech presentation or planned cesarean delivery with cephalic presentation had reduced fecundability compared with those who gave birth vaginally. Emergency cesarean delivery with cephalic presentation was not associated with fecundability.

Wesselink AK, Wise LA, Hatch EE, Rothman KJ, Mikkelsen EM, Stanford JB, McKinnon CJ, Mahalingaiah S. Menstrual cycle characteristics and fecundability in a North American preconception cohort. Ann Epidemiol 2016; 26(7): 482-7.e1.

Among North American pregnancy planners, women with shorter menstrual cycle lengths (≤26 days) had lower fecundability than women with menstrual cycles of 27-29 days. Women who had their first menstrual period at age <12 years had lower fecundability than women who had their first menstrual period at age 12-13 years. Duration and intensity of menstrual flow were not associated with fecundability.

Wesselink AK, Rothman KJ, Hatch EE, Mikkelsen EM, Sørensen HT, Wise LA. Age and fecundability in a North American preconception cohort study. Am J Obstet Gynecol 2017; 217(6): 667.e1-667.e8.

Among women, fecundability decreases with age in an approximately linear manner, with a slightly stronger decline after age ~37 years. After accounting for the age of the female partner, male age was not strongly related to fecundability; however, our study did not include many men over age 45.

McInerney KA, Hahn KA, Hatch EE, Mikkelsen EM, Steiner AZ, Rothman KJ, Sørensen HT, Snerum TM, Wise LA. Lubricant use during intercourse and time-to-pregnancy: a prospective cohort study. BJOG 2018; 125(12): 1541–1548.

Among North American pregnancy planners, lubricant use during intercourse was not associated with fecundability. This association was constant across types of lubricant, including water-based, oil-based, silicone-based and “fertility friendly” lubricants.

Stanford JB, Willis SK, Hatch EE, Rothman KJ, Wise LA. Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study. Fertil Steril 2019; 112(5): 892-899.

Among North American pregnancy planners, many used fertility indicators such as counting days or charting menstrual cycles, measuring basal body temperature, monitoring cervical fluid, using urine luteinizing hormone tests, or feeling for changes in position of the cervix. Use of any fertility indicators was associated with greater fecundability. We did not find consistent evidence of improved fecundability resulting from use of one specific fertility indicator over another.

Wildenschild C, Riis AH, Ehrenstein V, Hatch EE, Wise LA, Rothman KJ, Sørensen HT, Mikkelsen EM. Fecundability among Danish women with a history of miscarriage: a prospective cohort study. BMJ Open 2019; 9(1): e023996.

We compared the fecundability of Danish women who previously only had live births and those who previously only had miscarriages. Women who only had miscarriages took longer to conceive, but had a similar probability of conceiving within 12 cycles of pregnancy attempts.

Stanford JB, Willis SK, Hatch EE, Rothman KJ, Wise LA. Fecundability in relation to use of mobile computing apps to track the menstrual cycle. Hum Reprod 2020; 35(10): 2245-2252.

Use of a menstrual cycle tracking app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine luteinizing hormone), may increase fecundability by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved fecundability resulting from use of one specific app over another.

Willis SK, Matthew HM, Wise LA, Hatch EE, Wesselink AK, Rothman KJ, Mahalingaiah S. Menstrual patterns and self-reported hirsutism as assessed via the modified Ferriman-Gallwey scale: A cross-sectional study. Eur J Obstet Gynecol Reprod Biol 2020; 248: 137-143.

Hirsutism is the presence of excess hair in a male-like pattern, and may indicate an excess of androgen (a hormone). Among North American pregnancy planners, menstrual cycle characteristics including menstrual irregularity, longer cycle length, and heavier menstrual flow were associated with self-reported hirsutism.

Willis SK, Hatch EE, Wesselink AK, Rothman KJ, Mikkelsen EM, Ahrens KA, Wise LA. Post-partum interval and time to pregnancy in a prospective preconception cohort. Paediatr Perinat Epidemiol 2020; epub ahead of print.

Post-partum interval refers to the time between giving birth and attempting to conceive again. Among North American pregnancy planners, long post-partum intervals (≥48 months) were associated with slightly reduced fecundability, independent of female age. Short post-partum intervals (<12 months) were weakly associated with reduced fecundability in some groups, including women with a history of Caesarean delivery and planned pregnancies.

Wise LA, Wesselink AK, Hatch EE, Weuve J, Murray EJ, Wang TR, Mikkelsen EM, Sørensen HT, Rothman KJ. Changes in behavior with increasing pregnancy attempt time: a prospective cohort study. Epidemiology 2020; 31: 659–667.

We assessed how North American pregnancy planners changed their behaviors as pregnancy attempt time increases. Some common changes were reducing intake of caffeine, alcohol, and marijuana, and increasing activities to improve chances of conception (e.g., ovulation testing).

Yland JJ, Bresnick KA, Hatch EE, Wesselink AK, Mikkelsen EM, Rothman KJ, Sørensen HT, Huybrechts KF, Wise LA. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ 2020; 11: 371:m3966.

Among Danish and North American pregnancy planners, use of some hormonal contraceptive methods was associated with delays in return of fertility. Injectable contraceptives showed the longest delay (five to eight menstrual cycles). However, there was little lasting effect of long-term use of hormonal contraceptive methods on fecundability.