Correspondence
Pregnancy and the Timing of Intercourse
N Engl J Med 1996; 334:1266-1268May 9, 1996
- Article
To the Editor:
Wilcox et al. (Dec. 7 issue)1 reported that among 221 women who were attempting to become pregnant, conception occurred only during a six-day period that ended on the day of ovulation. This study provides excellent information for women who are trying to conceive. However, these data are probably not applicable to the large number of women who are trying to avoid pregnancy or having unprotected intercourse but who do not want to become pregnant. These women are much more likely to have intercourse outside the six-day fertile period and thus are more likely to conceive outside that period.
In order to determine the probability that intercourse on any day outside the six-day interval can result in pregnancy, it is necessary to examine menstrual cycles in which intercourse did not occur during those six days. Wilcox et al. reported that 31 of 625 menstrual cycles, or 5 percent, met this definition, and none resulted in conception. Indeed, they stated that they could not “exclude a probability of conception of up to 12 percent on either the seventh day before ovulation or the day after ovulation (95 percent confidence interval, 0 to 0.12).” We question whether their data are sufficient to exclude the possibility that conception may occur over a much broader range of days surrounding ovulation. It would be helpful to know how many women are represented by these 31 cycles and if and when intercourse occurred during each cycle. The power of these data to determine whether intercourse after ovulation can result in pregnancy is likely to be low.
Since approximately 50 percent of the pregnancies in the United States are not planned and since a large number of women may use the timing of ovulation to make decisions about contraception, it is important to obtain more accurate information about the likelihood of conceiving during each day of the menstrual cycle. Such information can best be obtained by studying a population-based cohort of women and examining a larger number of menstrual cycles in which intercourse did not occur during the six-day interval identified by Wilcox et al.
1 ReferencesD. Kim Waller, Ph.D.
Anne M. Sweeney, Ph.D.
University of Texas Health Science Center, Houston, TX 772251
Wilcox AJ ,Weinberg CR ,Baird DD . Timing of sexual intercourse in relation to ovulation -- effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995;333:1517-1521
Full Text | Web of Science | Medline
To the Editor:
Wilcox et al. concluded that “nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation.” This bold statement is very misleading, perhaps even wrong: the authors acknowledge that “we cannot exclude a probability of conception of up to 12 percent on . . . the day after ovulation.” Furthermore, the methods used are flawed: intercourse charted on the record provided each morning “was assumed to have occurred the previous day.”
In 1975, my colleagues and I published our analysis of the day of conception in women receiving fresh donor semen placed in a cervical cap.1 Ovulation was determined from records of basal body temperature. Although most conceptions occurred before or on the day of ovulation (33 of 45), consistent with the observations of Wilcox et al., 12 of 45 conceptions (27 percent) occurred in the two days after ovulation.
All tests for “ovulation” (based on urinary levels of luteinizing hormone or steroids or basal body temperature) measure events associated with release of the egg, and not the physical event itself. These tests are done only once every 24 hours. Thus, there is at least one day and probably several days of biologic variance in our “indirect measures.” Precision is further diminished by the fact that the length of survival of sperm and the length of time in which the egg can be fertilized are both uncertain. Therefore, the unqualified conclusion of Wilcox et al., which has been widely reported in the news media, has done a double disservice to our patients. Those attempting to become pregnant miss an opportunity because they stop coitus when their test shows that ovulation has occurred. Worse, couples using natural family planning will resume intercourse before the “safe” time has begun.
1 ReferencesRonald C. Strickler, M.D.
Washington University School of Medicine, St. Louis, MO 631101
Strickler RC ,Keller DW ,Warren JC . Artificial insemination with fresh donor semen. N Engl J Med 1975;293:848-853
Full Text | Web of Science | Medline
To the Editor:
As one who has worked in the field of natural family planning for over 20 years, I find it rewarding that Wilcox et al. have shown that pregnancy does not occur after the day of ovulation. That has been used as a principle in natural family planning for many years, and the strict basal-body-temperature system (which is a postovulatory method) has been referred to as a “highly reliable” means of avoiding pregnancy.
In 1978, my colleagues and I reported that the average length of the mucus cycle leading up to the peak day in the Billings ovulation method was 5.9 days.1 Ovulation occurred most frequently on the peak day, although there was a range around the time of the peak day when ovulation occurred. Nonetheless, it is of some interest that the average length of the mucus cycle coincides with the length of the six-day “window” described by Wilcox et al. Although these two concepts are not equivalent, there is some relation between them. Our study also involved healthy women.
What is perhaps more difficult to explain is the difference between their data and ours with regard to cumulative pregnancy rates in patients with apparently normal fertility using fertility-focused intercourse.2 The effectiveness of the ovulation method of natural family planning (a method based on the discharge of the normal cervical mucus produced up to the time of ovulation) to achieve a pregnancy was assessed with the use of a pregnancy rate based on fertility-focused intercourse that was compiled in a cumulative fashion from one cycle to the next. In our study, multiple acts of intercourse may have occurred during the course of the defined fertile time. Fifty consecutive patients were followed as they began using the method to become pregnant after having previously used it with 100 percent success to avoid pregnancy. Seventy-six percent of these patients became pregnant in the very first cycle of use. Ninety percent were pregnant by the third cycle, and 98 percent by the sixth cycle.
Similar results, showing an increased pregnancy rate as the peak day approached (66.7 percent), were obtained in the World Health Organization trials of the Billings ovulation method.3 Indeed, even Barrett and Marshall4 observed a 68 percent rate of pregnancy when the frequency of intercourse was increased to every day around the presumably fertile period.
These data are substantially different from those of Wilcox et al. and suggest that the efficiency of the human reproductive system is actually greater than previously thought.
4 ReferencesThomas W. Hilgers, M.D.
Creighton University School of Medicine, Omaha, NE 681781
Hilgers TW ,Abraham GE ,Cavanagh D . Natural family planning. I. The peak symptom and estimated time of ovulation. Obstet Gynecol 1978;52:575-582
Web of Science | Medline2
Hilgers TW ,Daly KD ,Prebil AM ,Hilgers SK . Cumulative pregnancy rates in patients with apparently normal fertility and fertility-focused intercourse. J Reprod Med 1992;10:864-8663
A prospective multicentre trial of the ovulation method of natural family planningIII. Characteristics of the menstrual cycle and fertile phases. Fertil Steril 1983;40:773-778
Web of Science | Medline4
Barrett JC ,Marshall J . The risk of conception on different days of the menstrual cycle. Popul Stud 1969;23:455-461
CrossRef
To the Editor:
The well-written editorial “Pregnancy and the Timing of Intercourse” by Dr. Simpson (Dec. 7 issue)1 contains two misstatements that should be corrected to avoid confusion. He states, “In none of the 192 pregnancies they studied did Wilcox et al. find evidence of conception after ovulation.” Conception is defined as fertilization of the oocyte by a spermatozoon to form a viable zygote.2 In nearly all mammalian species, fertilization occurs in the oviduct a few hours after ovulation takes place.3 In the primate the egg is picked up by the fimbriated end of the oviduct after it is completely extruded from the graafian follicle of the ovary.4 The ovum is then rapidly transported to the ampullary portion of the oviduct, where fertilization of the egg by a single spermatozoon occurs. Thus, conception in humans always occurs on the day of ovulation, not “usually . . . on the day of ovulation or one or two days before,” as stated in the editorial.
4 ReferencesDaniel R. Mishell, Jr., M.D.
University of Southern California School of Medicine, Los Angeles, CA 900331
Simpson JL . Pregnancy and the timing of intercourse. N Engl J Med 1995;333:1563-1565
Full Text | Web of Science | Medline2
Stedman's medical dictionary. 26th ed. Baltimore: Williams & Wilkins, 1995.
3
Pregnancy: overview and diagnosis: ovarian function and ovulation. In: Cunningham FG, MacDonald PC, Leveno KJ, Gant NF, Gilstrap LC III, eds. Williams obstetrics. 19th ed. Norwalk, Conn.: Appleton & Lange, 1993:18.
4
Eddy A ,Pauerstein CJ . Anatomy and physiology of the fallopian tube. Clin Obstet Gynecol 1980;23:1177-1193
CrossRef | Medline
Author/Editor Response
The authors reply:
To the Editor: The correspondents ask about the precision and generalizability of the six-day window of fertility reported in our paper. Our data came from women who were trying to become pregnant. Because such women typically have regular and frequent intercourse, they are likely by chance to have intercourse at least once during the most fertile days of the cycle. In our data, intercourse on days outside the six-day interval statistically contributed nothing to the chance of conception. If our statement that nearly all couples conceive during this six-day interval seems too bold to Dr. Strickler, perhaps it is because he overlooked the crucial first half of the sentence: “Among healthy women trying to conceive.”
However, the probability of conception outside this interval is not necessarily zero, a point underscored by Drs. Waller and Sweeney. A far larger study than ours would be required to pinpoint the small or nonexistent chance of conception outside this period. For that purpose, a more efficient alternative would be to study couples trying to avoid pregnancy by periodic abstinence.
Besides statistical precision, there is an issue of biologic precision. The use of basal body temperature to identify the day of ovulation is subject to considerable error.1 Therefore, studies based on the use of basal body temperature (such as the one by Dr. Strickler) will predictably find some conceptions attributed to intercourse on the days “after” ovulation. This can happen solely because of random error in identifying the day of ovulation.
The remarkably high rate of conception reported by Hilgers is not consistent with our data, nor with the subsequent reanalysis of data from a study he cites. The maximal rate of conception of 68 percent reported by Barrett and Marshall2 was later revised by Royston,3 who applied an extension of Barrett and Marshall's model to the same data and estimated a maximal conception rate of 38 percent.
Finally, we hope readers will distinguish between media versions of our findings and the findings themselves. We think our data bring us a step closer to describing the physiologic window of human fertility. However, in determining the day of ovulation, we had the advantage of using steroid patterns present before and after ovulation. It is easier to identify the day of ovulation retrospectively than prospectively. Before our findings can be fully translated into practice, better predictors and markers of the fertile interval are needed.
3 ReferencesAllen J. Wilcox, M.D., Ph.D.
Clarice R. Weinberg, Ph.D.
Donna D. Baird, Ph.D.
National Institute of Environmental Health Sciences, Research Triangle Park, NC 277091
Campbell KL . Methods of monitoring ovarian function and predicting ovulation: summary of a meeting. Res Front Fertil Regul 1985;3:1-16
Medline2
Barrett JC ,Marshall J . The risk of conception on different days of the menstrual cycle. Popul Stud 1969;23:455-461
CrossRef3
Royston JP . Basal body temperature, ovulation and the risk of conception, with special reference to the lifetimes of sperm and egg. Biometrics 1982;38:397-406
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Mishell is correct in wishing that parts of my editorial were more lucid. More precisely, we are concerned with determining the day of the coital event leading to conception, vis-à-vis the day of ovulation. Naturally, conception itself can only occur after ovulation; in traditional textbooks such as those cited by Mishell, conception is assumed to occur within 24 hours after ovulation. Dr. Mishell's statement that “conception in humans always occurs on the day of ovulation” could be taken to mean that he doubts the existence of delayed fertilization. However, an enormous body of data on animals and considerable circumstantial data on humans favor the possibility that a definite minority of conceptions occur days after ovulation (delayed fertilization).1,2 My colleagues and I found that 9.4 percent of 524 pregnancies resulted from coitus that took place one or more days after ovulation3 (Table 1Table 1
Pregnancy Rate According to the Day of Coitus, Based on 524 Pregnancies among Women Using Natural Family-Planning Methods.). Whether conception in such postovulatory circumstances increases the frequency of chromosomal abnormalities and other genetic defects is the question under consideration.1,4 To date, few deleterious effects associated with delayed fertilization have been found,5 but additional studies are needed.5 ReferencesJoe Leigh Simpson, M.D.
Baylor College of Medicine, Houston, TX 77030-34981
Simpson JL ,Gray RH ,Queenan JT , et al. Pregnancy outcome associated with natural family planning (NFP): scientific basis and experimental design for an international cohort study. Adv Contracept 1988;4:247-264
CrossRef | Medline2
James WH . Mongolism, delayed fertilization and human sexual behaviour. Nature 1968;219:279-280
CrossRef | Web of Science | Medline3
Simpson JL ,Gray RH ,Queenan JT , et al. Timing of intercourse. Hum Reprod 1995;10:2176-2177
Web of Science | Medline4
Wilcox AJ ,Weinberg CR ,Baird DD . Timing of sexual intercourse in relation to ovulation -- effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995;333:1517-1521
Full Text | Web of Science | Medline5
Gray RH ,Simpson JL ,Kambic RT , et al. Timing of conception and the risk of spontaneous abortion among pregnancies occurring during the use of natural family planning. Am J Obstet Gynecol 1995;172:1567-1572
CrossRef | Web of Science | Medline
