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OVULATION INDUCTION AND CONGENITAL MALFORMATIONS
961 ECTOPIC-PREGNANCY RATES BY PRIOR O.C. USE AND BY RISK
OVULATION INDUCTION AND CONGENITAL MALFORMATIONS
CATEGORIES
SIR,—Several case-reports have linked clomiphene with congenital malformations, especially neural-tube defects,1-5 so need to evaluate the possible teratogenicity of prepused to induce ovulation. Data from the record-linked Jerusalem Perinatal StUdy6 are reassuring. Mothers of 9886 babies have been questioned about clomiphene treatment as part of a retrospective post-partum interueBt on contraceptive use, fecundity, and other topics. The study covers three obstetric units and over 90% of births to Momen living in West Jerusalem. Data on malformations and maternal and infant morbidity and mortality are obtained in:here
is a
arations
dependently. A full report of the outcome of pregnancies after treatment induce ovulation will be published later, when data collection is complete. So far 225 babies have been born after clomiphene treatment at the time of conception, or shortly before, to
and 66 after human menopausal
gonadotrophin (H.M.G.).
Births before 28 weeks’ gestation were excluded. The frequency of multiple deliveries was 13% after clomiphene and 15% after H.M.G., and there was a slight, though not significant, excess of males. Mothers having treatment to induce ovulation were significantly older than the population as a whole, and more than half were also treated with hormones, mainly progestagens, in early pregnancy. 2 babies in the clomiphene-treated group had major malformations (8.9/1000), 1 with Down syndrome and 1 with imperforate anus; there were no neural-tube defects. This frequency of major malformations, and the additional 88.9/1000 with minor defects does not differ significantly from the 10.3 and 72.4/1000 reported for the population as a whole. There was no significant excess of any single minor malformation. After treatment with H.M.G. there was 1 major and 5 minor malformations (152 and 758/1000), close to the expected frequencies.
These preliminary data suggest that babies born after ovulainduction are little or no more at risk for malformations than the population as a whole. tion
Supported by
National
Institutes
of Health
contract
NOI-
HD-4-2853.
The corresponding rate among women who had used and discontinued o.c.s for any period of observation was 4-3/1000 (2 cases), the rates between the two groups being not significantly different. The first woman, 23 years of age, had a tubal pregnancy 13 months after o.c. discontinuation and 4 months after her first live birth. The other woman, a 29-year-old para 2, had her tubal pregnancy 18 months after she stopped using o.c.s. She resumed menses 38 days after her last pill withdrawal flow and then had sixteen menstrual periods with a mean cycle length of 28.9days and standard deviation of 1.8 days. It is difficult to implicate the prior use of o.c.s in either of these cases, nor was there evidence of "a temporary hormonal imbalance" as suggested by Weiss et al. Our findings of lower (but not statistically significantly different) rates for the incidence of ectopic gestation among prior users as compared with never-users of o.c.s persists whether the denominator is expressed in terms of number of women, number of live births, total number of pregnancies, or number of menstrual cycles during which no contraceptive use was recorded (table). Thus, we cannot concur with Dr Weiss and his colleagues’ hypothesis of "an after pill effect" on the occurrence of tubal pregnancy.
(7-4/1000).
-
Department of Medical Ecology, Hebrew
University-Hadassah Medical School,
Jerusalem, Israel
SUSAN HARLAP
ECTOPIC PREGNANCY AND THE PILL
SIR,—DR Weiss and his colleagues (July 24, p. 196) reported cases of tubal pregnancy which occurred "immediately" after discontinuation of oral contraceptive (o.c.) use, on the basis of which they proposed a cause-and-effect relationship. Without a description of the population of women at risk women in their catchment area who had discontinued o.c. use for a specified period of time) or presentation of comparable data for non-users of o.c.s, their conclusion that the 5 reported cases show "a high frequency of tubal pregnancy" is unsupportable. The authors’ speculations about possible mechanisms, therefore, also seem unwarranted. BBewish to report the experience of 869 young married ’omen included in the Menstruation and Reproduction Histown Research Program at the University of Minnesota and followed up prospectively between 1961 and 1970. During that decade, 463 women chose to use o.c.s, while 406 did not. 3 :;er-users underwent laparotomies for ectopic pregnancy J L , Kohler, H G Lancet, 1973, i, 1256 B ibid 1973, ii, 379 Barrett, C , Hakim, C ibid p 916 4 Field, B Kerr, C ibid 1974, ii, 1511. 5 Berman, P ibid 1975, ii, 878. 6 Davies,A M , and others Israel J med Sci 1969, 5, 1095.
International Fertility Research Research Triangle Park, North Carolina 27709, U.S.A. Menstruation and Reproduction History Research Program, Boynton Health Service, University of Minnesota
Program,
GARY S. BERGER ROBERT N. TAYLOR,
JR
ALAN E. TRELOAR
DIABETIC RETINOPATHY AND PROLACTIN
al.’ have shown in a short series (five diaretinopathy and 10 diabetics without severe retinopathy) that fasting serum-prolactin concentrations were normal, whereas diabetics without severe retinopathy had higher concentrations (mean 36.6 ng/ml). Using a commercial radioimmunoassay2 we measured serum-prolactin in 55 diabetics (32 females and 23 males) of whom 26 had severe retinopathy. The prolactin assay was done not only on fasting samples (blood-sample at 8 A.M.) but also on blood-samples drawn every 4 h over 24 h. Results were analysed by the distribution-free test of Mann and Whitney on the fasting levels and the sum of the six daily values. The mean prolactin concentration in retinopathic patients was 11.5 ng/ml with the 90th percentile at 21 ng/ml. In dia-
SIR;—Hunter
betics with
et
severe
1 Dyson,
2 Sandler,
3
1 2
Hunter, P. R., Anderson, J , Lunn, T A , Horrobin, D. F , Boyns, A. R., Cole, E N Lancet, 1974, i,1237. Reuter, A M., Kennes, F., Gevaert, Y., Franchimont, P Inc. J. nucl med. Biol. 1976, 3, 21.
OVULATION INDUCTION AND CONGENITAL MALFORMATIONS
CATEGORIES
SIR,—Several case-reports have linked clomiphene with congenital malformations, especially neural-tube defects,1-5 so need to evaluate the possible teratogenicity of prepused to induce ovulation. Data from the record-linked Jerusalem Perinatal StUdy6 are reassuring. Mothers of 9886 babies have been questioned about clomiphene treatment as part of a retrospective post-partum interueBt on contraceptive use, fecundity, and other topics. The study covers three obstetric units and over 90% of births to Momen living in West Jerusalem. Data on malformations and maternal and infant morbidity and mortality are obtained in:here
is a
arations
dependently. A full report of the outcome of pregnancies after treatment induce ovulation will be published later, when data collection is complete. So far 225 babies have been born after clomiphene treatment at the time of conception, or shortly before, to
and 66 after human menopausal
gonadotrophin (H.M.G.).
Births before 28 weeks’ gestation were excluded. The frequency of multiple deliveries was 13% after clomiphene and 15% after H.M.G., and there was a slight, though not significant, excess of males. Mothers having treatment to induce ovulation were significantly older than the population as a whole, and more than half were also treated with hormones, mainly progestagens, in early pregnancy. 2 babies in the clomiphene-treated group had major malformations (8.9/1000), 1 with Down syndrome and 1 with imperforate anus; there were no neural-tube defects. This frequency of major malformations, and the additional 88.9/1000 with minor defects does not differ significantly from the 10.3 and 72.4/1000 reported for the population as a whole. There was no significant excess of any single minor malformation. After treatment with H.M.G. there was 1 major and 5 minor malformations (152 and 758/1000), close to the expected frequencies.
These preliminary data suggest that babies born after ovulainduction are little or no more at risk for malformations than the population as a whole. tion
Supported by
National
Institutes
of Health
contract
NOI-
HD-4-2853.
The corresponding rate among women who had used and discontinued o.c.s for any period of observation was 4-3/1000 (2 cases), the rates between the two groups being not significantly different. The first woman, 23 years of age, had a tubal pregnancy 13 months after o.c. discontinuation and 4 months after her first live birth. The other woman, a 29-year-old para 2, had her tubal pregnancy 18 months after she stopped using o.c.s. She resumed menses 38 days after her last pill withdrawal flow and then had sixteen menstrual periods with a mean cycle length of 28.9days and standard deviation of 1.8 days. It is difficult to implicate the prior use of o.c.s in either of these cases, nor was there evidence of "a temporary hormonal imbalance" as suggested by Weiss et al. Our findings of lower (but not statistically significantly different) rates for the incidence of ectopic gestation among prior users as compared with never-users of o.c.s persists whether the denominator is expressed in terms of number of women, number of live births, total number of pregnancies, or number of menstrual cycles during which no contraceptive use was recorded (table). Thus, we cannot concur with Dr Weiss and his colleagues’ hypothesis of "an after pill effect" on the occurrence of tubal pregnancy.
(7-4/1000).
-
Department of Medical Ecology, Hebrew
University-Hadassah Medical School,
Jerusalem, Israel
SUSAN HARLAP
ECTOPIC PREGNANCY AND THE PILL
SIR,—DR Weiss and his colleagues (July 24, p. 196) reported cases of tubal pregnancy which occurred "immediately" after discontinuation of oral contraceptive (o.c.) use, on the basis of which they proposed a cause-and-effect relationship. Without a description of the population of women at risk women in their catchment area who had discontinued o.c. use for a specified period of time) or presentation of comparable data for non-users of o.c.s, their conclusion that the 5 reported cases show "a high frequency of tubal pregnancy" is unsupportable. The authors’ speculations about possible mechanisms, therefore, also seem unwarranted. BBewish to report the experience of 869 young married ’omen included in the Menstruation and Reproduction Histown Research Program at the University of Minnesota and followed up prospectively between 1961 and 1970. During that decade, 463 women chose to use o.c.s, while 406 did not. 3 :;er-users underwent laparotomies for ectopic pregnancy J L , Kohler, H G Lancet, 1973, i, 1256 B ibid 1973, ii, 379 Barrett, C , Hakim, C ibid p 916 4 Field, B Kerr, C ibid 1974, ii, 1511. 5 Berman, P ibid 1975, ii, 878. 6 Davies,A M , and others Israel J med Sci 1969, 5, 1095.
International Fertility Research Research Triangle Park, North Carolina 27709, U.S.A. Menstruation and Reproduction History Research Program, Boynton Health Service, University of Minnesota
Program,
GARY S. BERGER ROBERT N. TAYLOR,
JR
ALAN E. TRELOAR
DIABETIC RETINOPATHY AND PROLACTIN
al.’ have shown in a short series (five diaretinopathy and 10 diabetics without severe retinopathy) that fasting serum-prolactin concentrations were normal, whereas diabetics without severe retinopathy had higher concentrations (mean 36.6 ng/ml). Using a commercial radioimmunoassay2 we measured serum-prolactin in 55 diabetics (32 females and 23 males) of whom 26 had severe retinopathy. The prolactin assay was done not only on fasting samples (blood-sample at 8 A.M.) but also on blood-samples drawn every 4 h over 24 h. Results were analysed by the distribution-free test of Mann and Whitney on the fasting levels and the sum of the six daily values. The mean prolactin concentration in retinopathic patients was 11.5 ng/ml with the 90th percentile at 21 ng/ml. In dia-
SIR;—Hunter
betics with
et
severe
1 Dyson,
2 Sandler,
3
1 2
Hunter, P. R., Anderson, J , Lunn, T A , Horrobin, D. F , Boyns, A. R., Cole, E N Lancet, 1974, i,1237. Reuter, A M., Kennes, F., Gevaert, Y., Franchimont, P Inc. J. nucl med. Biol. 1976, 3, 21.