Int J Gynaecol Obstet 15: 133-136, 1977
Postcoital Hormonal Contraception: Uses, Risks, and Abuses A. Albert Yuzpe Department of Obstetrics and Gynaecology, University of Western Ontario, London, Canada
ABSTRACT Yuzpe, A. A. (Dept. of Obstetrics and Gynaecology, University of Western Ontario, London, Canada). Postcoital hormonal contraception: uses, risks, and abuses. Int J Gynaecol Obstet 15: 133-136, 1977 The author reviews the present state of use, risks, and side effects associated with postcoital hormonal contraceptives. Data pertaining to various regimens of postcoital hormonal contraception are presented.
INTRODUCTION The need for and interest in postcoital contraception is not unique to our times. Throughout the ages, women have used various concoctions, including herbal brews and potions (taken orally or administered vaginally), to prevent pregnancy. These concoctions were not only ineffective but often toxic. More recently, hormonal preparations and intrauterine devices proven effective as contraceptives have been investigated for effectiveness as postcoital measures. The following discussion will deal only with the use of hormonal preparations as postcoital contraceptive agents. USES OF POSTCOITAL CONTRACEPTIVES In some societies in South America, postcoital contraception is accepted as an ongoing method of contraception. Most North American physicians, however, consider the postcoital methods now available as strictly emergency measures. They are particularly valuable in cases of sexual assault or when conventional methods of contraception have failed, i.e., when condoms rupture or when defects are discovered in diaphragms. They may also be valuable for women who have infrequent intercourse. While physicians also agree that postcoital measures may be useful in protecting young women who fail to use contraceptives, part of their value in this instance is in bringing the young women to facilities where they can be counseled about
acceptable methods of ongoing contraception. Studies of university women, for example, show that their coital exposure is frequently either inadequately protected or totally unprotected (1, 15). RISKS FROM POSTCOITAL CONTRACEPTIVES Failure Reported failure rates vary, depending on the drug employed, the dosage, the time elapsed between coital exposure and treatment, and the possibility of other unprotected exposures outside of the time frame when the drug is (theoretically) effective. Estrogens, such as diethylstilbestrol (DES), ethinyl estradiol (EE) and conjugated estrogens (CE), as well as estrogen-progestogen combinations (e.g., EE and dl-norgestrel) have been used primarily as emergency (single treatment) postcoital contraceptives. Progestogens alone have been evaluated primarily as ongoing contraceptives administered after each coital exposure. It is difficult, therefore, to effectively compare these very different contraceptive modalities. Failure rates for the estrogen compounds vary from 0.0 to 2.4% (Table I). The majority of these studies have employed DES. In a recently completed study of a combined estrogenprogestogen regimen (EE and dl-norgestrel), we obtained a failure rate of 0.16% (Table II). This compares favorably with the estrogen-only compounds. Table I. Incidence of pregnancy following the administration of estrogen for postcoital contraception Type of Compound
Amount (mg)
Duration
Pregnancy Rate (%)
DES (7, 17)
50
od x 5
0.0-2.4
CE (2, 14)
10
tid x 6
0.0-1.1
EE (3,8)
2-5
od x 5
0.0-1.5
Int J Gynaecol Obstet 15
134 A. A. Yuzpe
Table I I . Incidence of pregnancy following the administrat i o n of an estrogen-progestogen compound for postcoital contraception Pregnancy Rate (%)
Drug and Dosage 0.1 mg EE + 1.0 mg dl-N
2.40
0.2 mg EE + 2.0 mg dl-N
0.16
Ethinyl estradiol and dl-norgestrel divided doses, 12 hours apart. Source: Yuzpe et al. (19, 20).
administered
in two
equally
Experience with administering progestogens as an ongoing method of contraception is far more extensive. Failure rates vary according to the compounds and dosages used. However, the method is user-dependent; therefore, it is difficult to assess the true rate of method failure. Reported failure rates vary from 0.6 to 38.0% for one compound evaluated, and from 0.0 to 45.2% for another. The higher failure rates in both cases, however, occurred with lower doses of the medication. At optimal dosage levels, the failure rates ranged from 1.0 to 3.5% (Table III). It is obvious from these results that method failure is a very real problem. However, even when the strictest of study criteria are imposed in evaluating these compounds, there is no doubt that the risk of pregnancy is greatly reduced. Systemic side effects Side effects are more common with the estrogenic compounds than with the progestogens or estrogen-progestogen combinations. Adverse reactions reported by estrogen users include nausea, vomiting, headache, dizziness, and breast tenderness. Using enteric coated DES tablets greatly decreased the incidence of gastrointestinal upset. In a recent evaluation of EE plus dl-norgestrel, two thirds of the patients had some nausea, but only Table I I I . Incidence of pregnancy following the administrat i o n of progestogen for postcoital contraception Dosage (mg)
Rate/100 Woman-Years
d-Norgestrel (4, 6)
1.00 0.40 0.30 0.25 0.15
0.0 3.5 6.7 6.2 45.2
Quingestanol acetate (13)
2.00 0.80 0.75 0.60
1.2 0.6 20.2 38.0
Type of Compound
Int J Gynaecol Obstet 15
19% had any vomiting (16). However, the number of patients evaluated for side effects in that study was very small. In other instances, a single dose of an antiemetic eliminated both the nausea and the vomiting. No other adverse effects were noted with the combined medication. Gastrointestinal upset was reported for less than 10% of the patients given only progestogen. However, these patients did report headaches, nervousness, and abdominal pain (6). Menstrual cycle changes The most frequent problem for progestogen users was a change in their menstrual patterns (6), particularly when progestogens were used as ongoing contraception. Teratogenicity The potential teratogenic effects of any postcoital hormonal medication on the fetus must be considered if the medication fails and the woman desires to continue the pregnancy to term. Hormones administered early in pregnancy, especially in the first month after conception, have been associated with limb-reduction defects and certain cardiovascular anomalies (5, 9). Although the definite effects of the various postcoital hormonal medications on the fetus are at present unknown, available data seem to indicate that terminating such a pregnancy is advisable. It would be difficult to defend the use of the medication without abortion backup. The argument that the medication would not affect the blastocyst to the same extent as it would a more developed embryo has been refuted by a study showing that the occurrence of limb-reduction defects was also increased among patients receiving oral contraceptives (OCs) at the time of conception, as well as among those receiving hormones in the first month after conception. The association between genital adenosis and adenocarcinoma in the offspring of women who received DES in early pregnancy is well known. Over 200 such cases have been reported. However, it appears that administering the medication to pregnant women before the sixth week of gestation does not produce the same effects that administering DES after that period does. Thus, the blastocyst appears to have a remarkable ability to withstand such hormonal effects and to continue its normal development (18). Furthermore, before the stage of organogenesis, these potential teratogens do not seem to affect a specific organ system. Animal studies further suggest that administering estrogen postcoitally has its effect primarily on the uterus, with secondary effects on the blastocyst (10-12). This would seem to nullify the teratogenic effect of the postcoital hormonal medication.
Postcoital hormonal contraception
Other risks When postcoital contraception fails, the resulting incidence of ectopic pregnancies is approximately 1 out of 10 pregnancies (14), compared to an incidence of approximately 1 out of 150 to 1 out of 200 (0.5%) when no contraception is used. This apparently high incidence of ectopic pregnancy is, however, misleading. Postcoital contraception seems to interfere with intrauterine pregnancies, but does not seem to have any effect upon the incidence of ectopic pregnancies. Thus, the total number of ectopic pregnancies observed are approximately equal in number to what would be expected if no contraception had been used.
135
CONCLUSION Several hormonal modalities of postcoital contraception are available. These include estrogens, progestogens, and a combination of the two. DES, until now, has proved to be the most successful, but it is associated with numerous side effects. According to two pilot studies, the combination of estrogen and progestogen may provide a viable alternative to the use of DES. However, the promotion of effective and acceptable ongoing methods of contraception should be the goal of all those who come into contact with patients who request postcoital contraception. REFERENCES
EVALUATING POSTCOITAL HORMONAL CONTRACEPTIVES Problems in evaluating postcoital hormonal contraceptives include the following: 1. The number of women who would actually have conceived if no postcoital medication had been administered cannot be determined. Selecting as subjects only those women exposed at midcycle and having positive postcoital tests would at least identify those at highest risk of becoming pregnant. 2. The fertility status of the woman treated and of her partner are often unknown. 3. The investigator must rely upon the accuracy of the patient's history to select or exclude her as a candidate for treatment. 4. The investigator must rely upon the patient to take the total dosage of medication, unless serious side effects occur. The smallest number of tablets possible, administered over the shortest period of time, should be an objective of any postcoital contraceptive regimen. 5. Most studies do not have a control group with which to compare the treatment group. 6. The moral and ethical implications of postfertilization contraception must also be considered because postcoital contraception does not appear to prevent fertilization, at least when used as an emergency measure.
ABUSES OF POSTCOITAL CONTRACEPTION Postcoital contraception should be reserved for emergency situations only; it should not be considered a viable alternative to routine, ongoing contraception. However, the postcoital administration of progestogens after each coital exposure is acceptable in some societies, despite the high incidence of menstrual irregularity associated with its use.
1. Bauman, K E: Selected aspects of the contraceptive practices of unmarried university students. Am J Obstet Gynecol 108:203, 1970. 2. Crist, T & Farrington, C: The use of estrogen as a post-coital contraceptive in North Carolina—trick or treatment. NC Med J 34:792, 1973. 3. Doring, G K: Morning-after-pill: die post-koitale hormonelle Schwangerschaftsverhutung (morning-after-pill: the postcoital hormonal protection against pregnancy). Deutsches Arzteblatt 35:2395, August 1971. 4. Echeverry, G & Sarria, C: Dosis altas de d-norgestrel como anti conceptivo post-coital (high doses of d-norgestrel as postcoital contraceptive), p. 5, 1974 (unpublished). 5. Janerick, D T, Piper, J M & Glebatis, D M: Oral contraceptives and congenital limb-reduction defects. N Engl J Med 291:691, 1974. 6. Kesseru, E, Larranaga, A & Parada, J: Post-coital contraception with d-norgestrel. Contraception 7:367, 1973. 7. Kuchera, L K: Post-coital contraception with diethylstilbestrol— updated. Contraception 70:47, 1974. 8. Lehfeldt, H: Choice of ethinyl estradiol as a post-coital pill (letter to the editor). Am J Obstet Gynecol 116:892, 1973. 9. Levy, E P, Cohen, A & Fraser, F C: Hormone treatment during pregnancy and congenital heart defects. Lancet 7:611, 1973. 10. Lutwak-Mann, C: Drugs and the blastocyst. In Fetal Pharmacology (ed. L Boreus), p. 419. Raven Press, New York, 1973. 11. Lutwak-Mann, C & Hay, M F: Effect on the early embryo of agents administered to the mother. Br Med J 2:944, 1962. 12. Lutwak-Mann, C, Hay, M F & New, D A T : Action of various agents on rabbit blastocysts in vivo and in vitro. J Reprod Fértil 7S.-235, 1969. 13. Mischler, T W, Berman, E, Rubio, B, Larranago, A, Guiloff, E & Moggia, A V: Further experience with quingestanol acetate as a post-coital oral contraceptive. Contraception S.-221, 1974. 14. Morris, J M & van Waganen, G: Interception: the use of post-ovulatory estrogens to prevent implantation. Am J Obstet Gynecol 775:101, 1973. 15. Munz, D, Carson, S, Brock, B, Bell, L, Kleinman, I, Robert, M & Simon, J: Contraception knowledge and practice among undergraduates at a Canadian university. Am J Obstet Gynecol 724:499, 1976. 16. Percival-Smith, R & Ross, A: Ethinyl estradiol dlnorgestrel combination as a morning-after-pill: preliminary report. BC Med J 18:240, 1976.
Int J Gynaecol Obstet 15
136 A. A. Yuzpe
17. Rosenfield, D L, Huggins, G R, Jusczyk, A M, Garcia, C R & Rickels, K: Medical, psychologic and social factors in morning-after-pill utilization. Paper presented at the 13th Annual Scientific Meeting of the Association of Planned Parenthood Physicians, Los Angeles, California, April 17-18, 1975. 18. Wilson, J G: Environment and Birth Defects, p. 305. Academic Press, New York, 1973. 19. Yuzpe, A A, Thurlow, H J, Ramzy, I & Leyshon, J I: Post-coital contraception—a pilot study. J Reprod Med 13:53, 1974. 20. Yuzpe, A A, Percival-Smith, R & Lancee, W J: Follow-up evaluation of a combination of ethinyl estradiol and dl-norgestrel as a post-coital contraceptive. Paper presented at the IX World Congress of Fertility and Sterility, Miami Beach, Florida, April 12-16, 1977.
Int J Gynaecol Obstet 15
Address for reprints: A. Albert Yuzpe Department of Obstetrics and Gynaecology University of Western Ontario London Canada
Postcoital Hormonal Contraception: Uses, Risks, and Abuses A. Albert Yuzpe Department of Obstetrics and Gynaecology, University of Western Ontario, London, Canada
ABSTRACT Yuzpe, A. A. (Dept. of Obstetrics and Gynaecology, University of Western Ontario, London, Canada). Postcoital hormonal contraception: uses, risks, and abuses. Int J Gynaecol Obstet 15: 133-136, 1977 The author reviews the present state of use, risks, and side effects associated with postcoital hormonal contraceptives. Data pertaining to various regimens of postcoital hormonal contraception are presented.
INTRODUCTION The need for and interest in postcoital contraception is not unique to our times. Throughout the ages, women have used various concoctions, including herbal brews and potions (taken orally or administered vaginally), to prevent pregnancy. These concoctions were not only ineffective but often toxic. More recently, hormonal preparations and intrauterine devices proven effective as contraceptives have been investigated for effectiveness as postcoital measures. The following discussion will deal only with the use of hormonal preparations as postcoital contraceptive agents. USES OF POSTCOITAL CONTRACEPTIVES In some societies in South America, postcoital contraception is accepted as an ongoing method of contraception. Most North American physicians, however, consider the postcoital methods now available as strictly emergency measures. They are particularly valuable in cases of sexual assault or when conventional methods of contraception have failed, i.e., when condoms rupture or when defects are discovered in diaphragms. They may also be valuable for women who have infrequent intercourse. While physicians also agree that postcoital measures may be useful in protecting young women who fail to use contraceptives, part of their value in this instance is in bringing the young women to facilities where they can be counseled about
acceptable methods of ongoing contraception. Studies of university women, for example, show that their coital exposure is frequently either inadequately protected or totally unprotected (1, 15). RISKS FROM POSTCOITAL CONTRACEPTIVES Failure Reported failure rates vary, depending on the drug employed, the dosage, the time elapsed between coital exposure and treatment, and the possibility of other unprotected exposures outside of the time frame when the drug is (theoretically) effective. Estrogens, such as diethylstilbestrol (DES), ethinyl estradiol (EE) and conjugated estrogens (CE), as well as estrogen-progestogen combinations (e.g., EE and dl-norgestrel) have been used primarily as emergency (single treatment) postcoital contraceptives. Progestogens alone have been evaluated primarily as ongoing contraceptives administered after each coital exposure. It is difficult, therefore, to effectively compare these very different contraceptive modalities. Failure rates for the estrogen compounds vary from 0.0 to 2.4% (Table I). The majority of these studies have employed DES. In a recently completed study of a combined estrogenprogestogen regimen (EE and dl-norgestrel), we obtained a failure rate of 0.16% (Table II). This compares favorably with the estrogen-only compounds. Table I. Incidence of pregnancy following the administration of estrogen for postcoital contraception Type of Compound
Amount (mg)
Duration
Pregnancy Rate (%)
DES (7, 17)
50
od x 5
0.0-2.4
CE (2, 14)
10
tid x 6
0.0-1.1
EE (3,8)
2-5
od x 5
0.0-1.5
Int J Gynaecol Obstet 15
134 A. A. Yuzpe
Table I I . Incidence of pregnancy following the administrat i o n of an estrogen-progestogen compound for postcoital contraception Pregnancy Rate (%)
Drug and Dosage 0.1 mg EE + 1.0 mg dl-N
2.40
0.2 mg EE + 2.0 mg dl-N
0.16
Ethinyl estradiol and dl-norgestrel divided doses, 12 hours apart. Source: Yuzpe et al. (19, 20).
administered
in two
equally
Experience with administering progestogens as an ongoing method of contraception is far more extensive. Failure rates vary according to the compounds and dosages used. However, the method is user-dependent; therefore, it is difficult to assess the true rate of method failure. Reported failure rates vary from 0.6 to 38.0% for one compound evaluated, and from 0.0 to 45.2% for another. The higher failure rates in both cases, however, occurred with lower doses of the medication. At optimal dosage levels, the failure rates ranged from 1.0 to 3.5% (Table III). It is obvious from these results that method failure is a very real problem. However, even when the strictest of study criteria are imposed in evaluating these compounds, there is no doubt that the risk of pregnancy is greatly reduced. Systemic side effects Side effects are more common with the estrogenic compounds than with the progestogens or estrogen-progestogen combinations. Adverse reactions reported by estrogen users include nausea, vomiting, headache, dizziness, and breast tenderness. Using enteric coated DES tablets greatly decreased the incidence of gastrointestinal upset. In a recent evaluation of EE plus dl-norgestrel, two thirds of the patients had some nausea, but only Table I I I . Incidence of pregnancy following the administrat i o n of progestogen for postcoital contraception Dosage (mg)
Rate/100 Woman-Years
d-Norgestrel (4, 6)
1.00 0.40 0.30 0.25 0.15
0.0 3.5 6.7 6.2 45.2
Quingestanol acetate (13)
2.00 0.80 0.75 0.60
1.2 0.6 20.2 38.0
Type of Compound
Int J Gynaecol Obstet 15
19% had any vomiting (16). However, the number of patients evaluated for side effects in that study was very small. In other instances, a single dose of an antiemetic eliminated both the nausea and the vomiting. No other adverse effects were noted with the combined medication. Gastrointestinal upset was reported for less than 10% of the patients given only progestogen. However, these patients did report headaches, nervousness, and abdominal pain (6). Menstrual cycle changes The most frequent problem for progestogen users was a change in their menstrual patterns (6), particularly when progestogens were used as ongoing contraception. Teratogenicity The potential teratogenic effects of any postcoital hormonal medication on the fetus must be considered if the medication fails and the woman desires to continue the pregnancy to term. Hormones administered early in pregnancy, especially in the first month after conception, have been associated with limb-reduction defects and certain cardiovascular anomalies (5, 9). Although the definite effects of the various postcoital hormonal medications on the fetus are at present unknown, available data seem to indicate that terminating such a pregnancy is advisable. It would be difficult to defend the use of the medication without abortion backup. The argument that the medication would not affect the blastocyst to the same extent as it would a more developed embryo has been refuted by a study showing that the occurrence of limb-reduction defects was also increased among patients receiving oral contraceptives (OCs) at the time of conception, as well as among those receiving hormones in the first month after conception. The association between genital adenosis and adenocarcinoma in the offspring of women who received DES in early pregnancy is well known. Over 200 such cases have been reported. However, it appears that administering the medication to pregnant women before the sixth week of gestation does not produce the same effects that administering DES after that period does. Thus, the blastocyst appears to have a remarkable ability to withstand such hormonal effects and to continue its normal development (18). Furthermore, before the stage of organogenesis, these potential teratogens do not seem to affect a specific organ system. Animal studies further suggest that administering estrogen postcoitally has its effect primarily on the uterus, with secondary effects on the blastocyst (10-12). This would seem to nullify the teratogenic effect of the postcoital hormonal medication.
Postcoital hormonal contraception
Other risks When postcoital contraception fails, the resulting incidence of ectopic pregnancies is approximately 1 out of 10 pregnancies (14), compared to an incidence of approximately 1 out of 150 to 1 out of 200 (0.5%) when no contraception is used. This apparently high incidence of ectopic pregnancy is, however, misleading. Postcoital contraception seems to interfere with intrauterine pregnancies, but does not seem to have any effect upon the incidence of ectopic pregnancies. Thus, the total number of ectopic pregnancies observed are approximately equal in number to what would be expected if no contraception had been used.
135
CONCLUSION Several hormonal modalities of postcoital contraception are available. These include estrogens, progestogens, and a combination of the two. DES, until now, has proved to be the most successful, but it is associated with numerous side effects. According to two pilot studies, the combination of estrogen and progestogen may provide a viable alternative to the use of DES. However, the promotion of effective and acceptable ongoing methods of contraception should be the goal of all those who come into contact with patients who request postcoital contraception. REFERENCES
EVALUATING POSTCOITAL HORMONAL CONTRACEPTIVES Problems in evaluating postcoital hormonal contraceptives include the following: 1. The number of women who would actually have conceived if no postcoital medication had been administered cannot be determined. Selecting as subjects only those women exposed at midcycle and having positive postcoital tests would at least identify those at highest risk of becoming pregnant. 2. The fertility status of the woman treated and of her partner are often unknown. 3. The investigator must rely upon the accuracy of the patient's history to select or exclude her as a candidate for treatment. 4. The investigator must rely upon the patient to take the total dosage of medication, unless serious side effects occur. The smallest number of tablets possible, administered over the shortest period of time, should be an objective of any postcoital contraceptive regimen. 5. Most studies do not have a control group with which to compare the treatment group. 6. The moral and ethical implications of postfertilization contraception must also be considered because postcoital contraception does not appear to prevent fertilization, at least when used as an emergency measure.
ABUSES OF POSTCOITAL CONTRACEPTION Postcoital contraception should be reserved for emergency situations only; it should not be considered a viable alternative to routine, ongoing contraception. However, the postcoital administration of progestogens after each coital exposure is acceptable in some societies, despite the high incidence of menstrual irregularity associated with its use.
1. Bauman, K E: Selected aspects of the contraceptive practices of unmarried university students. Am J Obstet Gynecol 108:203, 1970. 2. Crist, T & Farrington, C: The use of estrogen as a post-coital contraceptive in North Carolina—trick or treatment. NC Med J 34:792, 1973. 3. Doring, G K: Morning-after-pill: die post-koitale hormonelle Schwangerschaftsverhutung (morning-after-pill: the postcoital hormonal protection against pregnancy). Deutsches Arzteblatt 35:2395, August 1971. 4. Echeverry, G & Sarria, C: Dosis altas de d-norgestrel como anti conceptivo post-coital (high doses of d-norgestrel as postcoital contraceptive), p. 5, 1974 (unpublished). 5. Janerick, D T, Piper, J M & Glebatis, D M: Oral contraceptives and congenital limb-reduction defects. N Engl J Med 291:691, 1974. 6. Kesseru, E, Larranaga, A & Parada, J: Post-coital contraception with d-norgestrel. Contraception 7:367, 1973. 7. Kuchera, L K: Post-coital contraception with diethylstilbestrol— updated. Contraception 70:47, 1974. 8. Lehfeldt, H: Choice of ethinyl estradiol as a post-coital pill (letter to the editor). Am J Obstet Gynecol 116:892, 1973. 9. Levy, E P, Cohen, A & Fraser, F C: Hormone treatment during pregnancy and congenital heart defects. Lancet 7:611, 1973. 10. Lutwak-Mann, C: Drugs and the blastocyst. In Fetal Pharmacology (ed. L Boreus), p. 419. Raven Press, New York, 1973. 11. Lutwak-Mann, C & Hay, M F: Effect on the early embryo of agents administered to the mother. Br Med J 2:944, 1962. 12. Lutwak-Mann, C, Hay, M F & New, D A T : Action of various agents on rabbit blastocysts in vivo and in vitro. J Reprod Fértil 7S.-235, 1969. 13. Mischler, T W, Berman, E, Rubio, B, Larranago, A, Guiloff, E & Moggia, A V: Further experience with quingestanol acetate as a post-coital oral contraceptive. Contraception S.-221, 1974. 14. Morris, J M & van Waganen, G: Interception: the use of post-ovulatory estrogens to prevent implantation. Am J Obstet Gynecol 775:101, 1973. 15. Munz, D, Carson, S, Brock, B, Bell, L, Kleinman, I, Robert, M & Simon, J: Contraception knowledge and practice among undergraduates at a Canadian university. Am J Obstet Gynecol 724:499, 1976. 16. Percival-Smith, R & Ross, A: Ethinyl estradiol dlnorgestrel combination as a morning-after-pill: preliminary report. BC Med J 18:240, 1976.
Int J Gynaecol Obstet 15
136 A. A. Yuzpe
17. Rosenfield, D L, Huggins, G R, Jusczyk, A M, Garcia, C R & Rickels, K: Medical, psychologic and social factors in morning-after-pill utilization. Paper presented at the 13th Annual Scientific Meeting of the Association of Planned Parenthood Physicians, Los Angeles, California, April 17-18, 1975. 18. Wilson, J G: Environment and Birth Defects, p. 305. Academic Press, New York, 1973. 19. Yuzpe, A A, Thurlow, H J, Ramzy, I & Leyshon, J I: Post-coital contraception—a pilot study. J Reprod Med 13:53, 1974. 20. Yuzpe, A A, Percival-Smith, R & Lancee, W J: Follow-up evaluation of a combination of ethinyl estradiol and dl-norgestrel as a post-coital contraceptive. Paper presented at the IX World Congress of Fertility and Sterility, Miami Beach, Florida, April 12-16, 1977.
Int J Gynaecol Obstet 15
Address for reprints: A. Albert Yuzpe Department of Obstetrics and Gynaecology University of Western Ontario London Canada
