Genital mycoplasmas and birth weight in offspring of primigravid women R. F. HARRISON, F.R.C.S.(Ed.)* ROSALINDE HURLEY, M.D.
J.
DELOUVOIS, PH.D.
London, England The relationship between colonization of pregnant women by Ureaplasma and Mycoplasma and the outcome of pregnancy in a study of 104 women is reported. There were eight abortions but no multiple births or stillbirths. Excluding abortions, the mean gestational length was 39.6 weeks and the corrected mean birth weight was 3.28 kilograms. There was no relationship between maternal colonization by genital mycoplasmas and reduction in birth weight of the offspring, but five of the eight women who aborted harbored Ureaplasma, suggesting an increased trend toward abortion in women harboring Ureaplasma. (AM. J. 0BSTET. GYNECOL. 133:201, 1979.)
IN 1976, McCormack 1 commented that the chain of events linking genital mycoplasmas to birth weight and to spontaneous abortion began about 15 years ago. The issue is still unresolved, although the premise appears to be straightforward. Klein and associates 2 observed that newborn infants were colonized with mycoplasmas in inverse relation to their birth weight. In order to ascertain the relationship between the presence of mycoplasmas in the cervix and urine and the outcome of pregnancy, Braun and colleagues 3 studied pregnant women prospectively tabulating their findings for 484 infants. They observed that babies born of women who harbored Ureaplasma (T-str.:~in mycoplasmas) at the first clinic visit had a mean birth weight that was 202 grams less than that of those born of women from whom Ureaplasma was not isolated. The association was independent of shortened gestational length and of known risk factors for low birth weight, including race. They believed, however, that factors other than simple colonization, possibly invasion by the microbes, were of importance in determining low birth weight since, although 79 per cent of pregnant women harbor From the lmtitute of Obstetrics and Gynaecology, University of London, and Queen Charlotte's Hospital for Women. Received for publication july 21, 1977. Accepted April27, 1978. Reprint requesL1: Dr. Rosalinde Hurley, Queen Charlotte's Maternity Hospital, Goldhawk Road, London, Englflnd W6 OXG.
*Present address: Department of Obstetrics and Gynaecology, Rotunda Hospital, Dublin. 0002-9378/79/020201 +03$00.30/0
©
1979 The C. V. Mosby Co.
Ureaplasma, 4 only 8.5 per cent of the babies in Braun and associates' series weighed less than 2.50 kilograms. It has been suggested by McCormack 1 that controlled treatment studies with antibiotics from the twentyeighth week of pregnancy until term might elucidate the role of the genital mycoplasmas in relation to birth weight. We report the relationship between colonization of pregnant women by Ureaplasma and Mycoplasma and the outcome of pregnancy in a study of 104 women.
Materials and methods The 104 primigravid women studied were randomly selected. Swabs from the vagina and cervix were taken at the first antenatal (booking) visit and examined microbiologically for Ureaplasma and Mycoplasma by means of methods described elsewhere. 5 Maternal height and midpregnancy weight were recorded, as was the outcome of pregnancy and the birth weight of the infant. The latter was corrected for sex, maternal height, and mid pregnancy weight using the conversion charts of Tanner and Thomson, 6 and statistical analyses were prepared using both corrected and uncorrected figures for birth weight. Results Six of 104 women m the study defaulted. Eight aborted and 90 were delivered of 90 infants: there were 39 live-born boys and 51 live-born girls. There were no multiple births or stillbirths. The weight of the abortuses was not analyzed in this study, since it could not always be measured accurately. 201
202
Harrison, Hurley, and delouvois
Am.
No. of infants
Birth weight (kg.) !±S.D.)
Gestational age (wk.) (±S.D.)
Corrected birth weight (kg.) (±S.D.!
47
3.30 0 58 2.83 3.43 0.39 3.22 0.42
39.56 1.39 39.00 39.RO 1.52 39.16 1.50 39.61 1.43
3.33 O.SR 2.73 3.37 0.36 3.17 0.40 3.28 0.19
2 3
I 33
4
9
All
90
3.37
0.50
*Group 1 negative; Group 2 positive for M. hommis only; Group 3 positive for Creaplasma only; Group 4 positive for M. hominis and Ureaplasma.
Group*
No. oj infanLI
Birth weight (kg.) (±S.D.)
Gestational age (wk.) (±S.D.)
Corrected birth weight (kg) (±S.D.)
45
3.39 0.57
39.65 1.24
:).2H 0.56
:H6
39.95 !.57 39.29 !.55
2 3
()
2H
()..}()
3.2.~
4
0.44
H
Birth weight Corrected Birth weight Gestational age
0.625 0.748 0.752
VI
V2
p
2 2
86 86 86
N.S. N.S. N.S.
22
Standard deviation corrected for size of sample. N .S. = not statistically significant.
We have included in the aborted group one live-born fetus of 24 weeks' gestation, weighing 595 grams, that survived ll Y2 hours. Apart from this fetus, only five babies, two of whom were delivered by cesarean section, weighed 2.50 kilograms or less. and of these. two were also small for dates; a further three babies, weighing more than 2.50 kilograms, were also small for dates, totalling five altogether. Of the 98 women whose pregnancies were studied until delivery, 4 7 harbored Ureaplasma and 10 harbored Mycoplasma lwmini.1. Thirty-eight women harbored Ureaplasma only, one harbored M. lwminis only, 9 harbored both, and :)0 harbored neither. Five of eight women who aborted, including the woman bearing the live-born fetus of 24 weeks, harbored Ureaplasma. Table l summarizes the duration of pregnancy and the birth weights of living and stillborn infants, including those born by cesarean section, born of women whose lower genital tract was cultured at the first antenatal visit. The patients are grouped according to the presence or absence of Ureaplasmas or Mycoplasmas. The mean gestational length \vas 39.6 \Veeks, and there is no statistically significant difference in gestational age among the four groups. The mean birth weight was 3.37 kilograms, and the mean birth weight corrected for sex, maternal height. and midpregnancy
:l.38
run 3.23 0.40
Standard deviation corrected for size of sample. *See Table I for code.
Table IV. Percentage incidence of Ureaplasma and M. hominis in 98 pregnant women in relation to the outcome of pregnancy
Table II. Analysis of variance for Groups l, 3, and 4 F. value
.January 15. 1979 Ohstct. Cvn2,500 kg. Live birth ,;;2,500 kg. Abortion
86 (44)
J
Positive
.\1. hominis
Negative
l
Positive
72 (34)
ill (71)
70 (7)
II\ \ ...
,
.119\ .._ \'-1
"-) 19\
""'", ..... ,
J(l ,..._, II\ ..._,
c~sarean
6 (:{) 6 (3)
II (5) 13 (6)
9 (8) 8 (7)
0 (0) :20 (2)
section Totals
100 (51)
100 (47)
100 (8H)
100 (10)
l)
....
*Figures in parentheses indicate number of patients.
weight was 3. 21'1 kiloqrams. There was no statistically significant variation in birth weight either mrrectFrl or uncorrected, in the four groups. as shown by two-sided T-tests or by analysis of variance (Table II). Standard deviation was corrected for the size of the sample. Table Ill shows the results of analysis excluding babies born by cesarean section. There is no significant difference in birth weight or in mean gestational age among the four groups. Table IV shows the incidence of Creaplasma and Mycoplasma at the first booking visit relative to the outcome of pregnancy. There was a tendency for Ureaplasma to be harbored more frequently by those who aborted. Only five babies in this series weighed 2.50 kilograms or less and were thus of low birth weight. Of these, one was born of a woman harboting Ureaplasma and one of a woman harboring both Ureaplasma and Af. hominis. Five babies, including two of lo'n' birth ·weight (,;2.50 kilograms), were small for dates. In each case risk factors accepted as relating to sma!! for dates were present and in only one case was the baby horn of a mother harboring Ureaplasma. The risk factors in-
Volume 133 Number 2
eluded late booking, maternal age, hypertension, anemia and antepartum hemorrhage, intrauterine growth retardation, and congenital cardiac malformation of the fetus. There was, therefore, no association between maternal carriage of Ureaplasma or Mycoplasma and low birth weight or small for date babies.
Comment We did not demonstrate any relationship between maternal colonization with genital mycoplasmas and reduced birth weight of offspring. The mean birth weight, even when corrected for maternal height and weight, did not differ in babies born of women who harbor Ureaplasma, Mycoplasma, both, or neither. The incidence of babies of low birth weight (,;;;;2.50 kilograms) in the series studied was 5 per cent, that of small for dates babies was also 5 per cent, and that of low-birth-weight babies who were also small for dates was 2 per cent. The numbers are too few to make a statistical analysis within these groups, but there is no trend toward their greater occurrence in women harboring genital mycoplasmas. Unlike other observers, 3 • 7 we did not find reduction in birth weight in babies born of women harboring genital mycoplasmas. Even if verifiable, reduction of birth weight is of no clinical consequence, unless it is accompanied by significant increase in the numbers of babies born who are of low birth weight ( ,;;;;2.50 kilograms) or small for dates.
Genital mycoplasmas and birth weight
203
Five of the eight women who aborted harbored Ureaplasma. di Musto and associates 7 noted, as did Braun and colleagues, 3 that the average birth weight of infants born of women harboring mycoplasmas was lower than in control groups but found no difference in the abortion rates. Pease and co-workers 8 isolated M. hominis type l from the otherwise sterile lung of a newborn infant, and commented that vaginal mycoplasmas could not be regarded as beyond the suspicion of pathogenicity to the human fetus. Jones 9 isolated M. hominis from the lungs of five of 62 aborted fetuses in the absence of bacterial pathogens or viruses and suggested that the organism may be capable of infecting a living fetus. Driscoll and associates 10 suggested that mycoplasmas may be responsible for unexplained, sometimes recurrent, human miscarriages. It has also been suggested that Urea plasma may be etiologically related to spontaneous abortionsY· 12 Thus, although none has proved the relationship. many observers have postulated mycoplasma infection as a cause, either primary or contributory, of abortion in human beings. Mycoplasmas c.an be eradicated from the genital tract easily. 13 In view of this, it is important that their role in spontaneous abortion, if any, be established speedily and beyond doubt. We are grateful to Mrs. analyses.
J.
Verrier for the statistical
REFERENCES I. McCormack, W. M.: Genital mycoplasmal infections: Their relation to prematurity and other abnormalities of reproduction, in Hurley R., editor: The pathology of pregnancy, Royal College of Pathologists Symposium, 1976, B. M.A. Publications. 2. Klein, J. 0., Buckland, D., and Finland, M.: Colonization of newborn infants by mycoplasmas, N. Engl. J. Med. 280: 1025, 1969. 3. Braun. P., Lee, Y. H., Klein, J. 0., Marcy, S. M., Klein, T. A.. Charles, D., Levy, P., and Kass, E. H.: Birth weight and genital mycoplasmas in pregnancy, N. Engl. J. Med. 284: 167, 1971. 4. Braun. P .. Klein, J. 0., Lee, Y. H., Marcy. S. M., Klein, T. A., Charles, D., Levy, P., and Kass, E. H.: Methodologic investigations and prevalence of genital mycoplasmas in pregnancy, J. Infect. Dis. 121: 391, 1970. 5. de Louvois, J., Blades, M., Harrison, R. F., Hurley, R., and Stanley, V. C.: Frequency of mycoplasma in fertile and infertile couples, Lancet 2: 1073, 1974. 6. Tanner.]. M.. and Thomson, A.M.: Standards for bilth weight at gestation periods from 32-42 weeks, allowing for maternal height and weight. Arch. Dis. Child. 45: 566, 1970.
7. di Musto, J. C., Bohjalian, 0., and Millar, M.: Mycoplasma hominis type 1 infection and pregnancy, Obstet. Gynaecol. 41: 33, 1973. 8. Pease, P., Rogers, K. B., and Cole, B. C.: A cytopathogenic strain of Mycoplasma hominis type 1 isolated from the lungs of a stillborn infant, J. Path. Bact. 94: 460. 1967. 9. Jones, D. M.: Mycoplasma hominis in abortion. Br. Med. J. 1: 338, 1967. 10. Driscoll, S. G., Kundsin, R. B .. Horne, H. W., Jr., and Scott, J. M.: Infections and first trimester losses: Possible role of mycoplasmas, Fettil. Steril. 20: 1017, 1969. 11. Kundsin, R. B., Driscoll, S. G., and Ming. P. L.: Strain of mycoplasma associated with human reproductive failure, Science 157: 1573, 1967. 12. Kundsin, R. B .. and Driscoll, S. G.: Mycoplasmas and human reproductive failure, Surg. Gynecol. Obstet. 131: 89, 1970. 13. Harrison. R. F., deLouvois.J ., Blades, M., and Hurley. R.: Doxycycline treatment and human infertility. Lancet 1: 605, 1975.
J.
DELOUVOIS, PH.D.
London, England The relationship between colonization of pregnant women by Ureaplasma and Mycoplasma and the outcome of pregnancy in a study of 104 women is reported. There were eight abortions but no multiple births or stillbirths. Excluding abortions, the mean gestational length was 39.6 weeks and the corrected mean birth weight was 3.28 kilograms. There was no relationship between maternal colonization by genital mycoplasmas and reduction in birth weight of the offspring, but five of the eight women who aborted harbored Ureaplasma, suggesting an increased trend toward abortion in women harboring Ureaplasma. (AM. J. 0BSTET. GYNECOL. 133:201, 1979.)
IN 1976, McCormack 1 commented that the chain of events linking genital mycoplasmas to birth weight and to spontaneous abortion began about 15 years ago. The issue is still unresolved, although the premise appears to be straightforward. Klein and associates 2 observed that newborn infants were colonized with mycoplasmas in inverse relation to their birth weight. In order to ascertain the relationship between the presence of mycoplasmas in the cervix and urine and the outcome of pregnancy, Braun and colleagues 3 studied pregnant women prospectively tabulating their findings for 484 infants. They observed that babies born of women who harbored Ureaplasma (T-str.:~in mycoplasmas) at the first clinic visit had a mean birth weight that was 202 grams less than that of those born of women from whom Ureaplasma was not isolated. The association was independent of shortened gestational length and of known risk factors for low birth weight, including race. They believed, however, that factors other than simple colonization, possibly invasion by the microbes, were of importance in determining low birth weight since, although 79 per cent of pregnant women harbor From the lmtitute of Obstetrics and Gynaecology, University of London, and Queen Charlotte's Hospital for Women. Received for publication july 21, 1977. Accepted April27, 1978. Reprint requesL1: Dr. Rosalinde Hurley, Queen Charlotte's Maternity Hospital, Goldhawk Road, London, Englflnd W6 OXG.
*Present address: Department of Obstetrics and Gynaecology, Rotunda Hospital, Dublin. 0002-9378/79/020201 +03$00.30/0
©
1979 The C. V. Mosby Co.
Ureaplasma, 4 only 8.5 per cent of the babies in Braun and associates' series weighed less than 2.50 kilograms. It has been suggested by McCormack 1 that controlled treatment studies with antibiotics from the twentyeighth week of pregnancy until term might elucidate the role of the genital mycoplasmas in relation to birth weight. We report the relationship between colonization of pregnant women by Ureaplasma and Mycoplasma and the outcome of pregnancy in a study of 104 women.
Materials and methods The 104 primigravid women studied were randomly selected. Swabs from the vagina and cervix were taken at the first antenatal (booking) visit and examined microbiologically for Ureaplasma and Mycoplasma by means of methods described elsewhere. 5 Maternal height and midpregnancy weight were recorded, as was the outcome of pregnancy and the birth weight of the infant. The latter was corrected for sex, maternal height, and mid pregnancy weight using the conversion charts of Tanner and Thomson, 6 and statistical analyses were prepared using both corrected and uncorrected figures for birth weight. Results Six of 104 women m the study defaulted. Eight aborted and 90 were delivered of 90 infants: there were 39 live-born boys and 51 live-born girls. There were no multiple births or stillbirths. The weight of the abortuses was not analyzed in this study, since it could not always be measured accurately. 201
202
Harrison, Hurley, and delouvois
Am.
No. of infants
Birth weight (kg.) !±S.D.)
Gestational age (wk.) (±S.D.)
Corrected birth weight (kg.) (±S.D.!
47
3.30 0 58 2.83 3.43 0.39 3.22 0.42
39.56 1.39 39.00 39.RO 1.52 39.16 1.50 39.61 1.43
3.33 O.SR 2.73 3.37 0.36 3.17 0.40 3.28 0.19
2 3
I 33
4
9
All
90
3.37
0.50
*Group 1 negative; Group 2 positive for M. hommis only; Group 3 positive for Creaplasma only; Group 4 positive for M. hominis and Ureaplasma.
Group*
No. oj infanLI
Birth weight (kg.) (±S.D.)
Gestational age (wk.) (±S.D.)
Corrected birth weight (kg) (±S.D.)
45
3.39 0.57
39.65 1.24
:).2H 0.56
:H6
39.95 !.57 39.29 !.55
2 3
()
2H
()..}()
3.2.~
4
0.44
H
Birth weight Corrected Birth weight Gestational age
0.625 0.748 0.752
VI
V2
p
2 2
86 86 86
N.S. N.S. N.S.
22
Standard deviation corrected for size of sample. N .S. = not statistically significant.
We have included in the aborted group one live-born fetus of 24 weeks' gestation, weighing 595 grams, that survived ll Y2 hours. Apart from this fetus, only five babies, two of whom were delivered by cesarean section, weighed 2.50 kilograms or less. and of these. two were also small for dates; a further three babies, weighing more than 2.50 kilograms, were also small for dates, totalling five altogether. Of the 98 women whose pregnancies were studied until delivery, 4 7 harbored Ureaplasma and 10 harbored Mycoplasma lwmini.1. Thirty-eight women harbored Ureaplasma only, one harbored M. lwminis only, 9 harbored both, and :)0 harbored neither. Five of eight women who aborted, including the woman bearing the live-born fetus of 24 weeks, harbored Ureaplasma. Table l summarizes the duration of pregnancy and the birth weights of living and stillborn infants, including those born by cesarean section, born of women whose lower genital tract was cultured at the first antenatal visit. The patients are grouped according to the presence or absence of Ureaplasmas or Mycoplasmas. The mean gestational length \vas 39.6 \Veeks, and there is no statistically significant difference in gestational age among the four groups. The mean birth weight was 3.37 kilograms, and the mean birth weight corrected for sex, maternal height. and midpregnancy
:l.38
run 3.23 0.40
Standard deviation corrected for size of sample. *See Table I for code.
Table IV. Percentage incidence of Ureaplasma and M. hominis in 98 pregnant women in relation to the outcome of pregnancy
Table II. Analysis of variance for Groups l, 3, and 4 F. value
.January 15. 1979 Ohstct. Cvn2,500 kg. Live birth ,;;2,500 kg. Abortion
86 (44)
J
Positive
.\1. hominis
Negative
l
Positive
72 (34)
ill (71)
70 (7)
II\ \ ...
,
.119\ .._ \'-1
"-) 19\
""'", ..... ,
J(l ,..._, II\ ..._,
c~sarean
6 (:{) 6 (3)
II (5) 13 (6)
9 (8) 8 (7)
0 (0) :20 (2)
section Totals
100 (51)
100 (47)
100 (8H)
100 (10)
l)
....
*Figures in parentheses indicate number of patients.
weight was 3. 21'1 kiloqrams. There was no statistically significant variation in birth weight either mrrectFrl or uncorrected, in the four groups. as shown by two-sided T-tests or by analysis of variance (Table II). Standard deviation was corrected for the size of the sample. Table Ill shows the results of analysis excluding babies born by cesarean section. There is no significant difference in birth weight or in mean gestational age among the four groups. Table IV shows the incidence of Creaplasma and Mycoplasma at the first booking visit relative to the outcome of pregnancy. There was a tendency for Ureaplasma to be harbored more frequently by those who aborted. Only five babies in this series weighed 2.50 kilograms or less and were thus of low birth weight. Of these, one was born of a woman harboting Ureaplasma and one of a woman harboring both Ureaplasma and Af. hominis. Five babies, including two of lo'n' birth ·weight (,;2.50 kilograms), were small for dates. In each case risk factors accepted as relating to sma!! for dates were present and in only one case was the baby horn of a mother harboring Ureaplasma. The risk factors in-
Volume 133 Number 2
eluded late booking, maternal age, hypertension, anemia and antepartum hemorrhage, intrauterine growth retardation, and congenital cardiac malformation of the fetus. There was, therefore, no association between maternal carriage of Ureaplasma or Mycoplasma and low birth weight or small for date babies.
Comment We did not demonstrate any relationship between maternal colonization with genital mycoplasmas and reduced birth weight of offspring. The mean birth weight, even when corrected for maternal height and weight, did not differ in babies born of women who harbor Ureaplasma, Mycoplasma, both, or neither. The incidence of babies of low birth weight (,;;;;2.50 kilograms) in the series studied was 5 per cent, that of small for dates babies was also 5 per cent, and that of low-birth-weight babies who were also small for dates was 2 per cent. The numbers are too few to make a statistical analysis within these groups, but there is no trend toward their greater occurrence in women harboring genital mycoplasmas. Unlike other observers, 3 • 7 we did not find reduction in birth weight in babies born of women harboring genital mycoplasmas. Even if verifiable, reduction of birth weight is of no clinical consequence, unless it is accompanied by significant increase in the numbers of babies born who are of low birth weight ( ,;;;;2.50 kilograms) or small for dates.
Genital mycoplasmas and birth weight
203
Five of the eight women who aborted harbored Ureaplasma. di Musto and associates 7 noted, as did Braun and colleagues, 3 that the average birth weight of infants born of women harboring mycoplasmas was lower than in control groups but found no difference in the abortion rates. Pease and co-workers 8 isolated M. hominis type l from the otherwise sterile lung of a newborn infant, and commented that vaginal mycoplasmas could not be regarded as beyond the suspicion of pathogenicity to the human fetus. Jones 9 isolated M. hominis from the lungs of five of 62 aborted fetuses in the absence of bacterial pathogens or viruses and suggested that the organism may be capable of infecting a living fetus. Driscoll and associates 10 suggested that mycoplasmas may be responsible for unexplained, sometimes recurrent, human miscarriages. It has also been suggested that Urea plasma may be etiologically related to spontaneous abortionsY· 12 Thus, although none has proved the relationship. many observers have postulated mycoplasma infection as a cause, either primary or contributory, of abortion in human beings. Mycoplasmas c.an be eradicated from the genital tract easily. 13 In view of this, it is important that their role in spontaneous abortion, if any, be established speedily and beyond doubt. We are grateful to Mrs. analyses.
J.
Verrier for the statistical
REFERENCES I. McCormack, W. M.: Genital mycoplasmal infections: Their relation to prematurity and other abnormalities of reproduction, in Hurley R., editor: The pathology of pregnancy, Royal College of Pathologists Symposium, 1976, B. M.A. Publications. 2. Klein, J. 0., Buckland, D., and Finland, M.: Colonization of newborn infants by mycoplasmas, N. Engl. J. Med. 280: 1025, 1969. 3. Braun. P., Lee, Y. H., Klein, J. 0., Marcy, S. M., Klein, T. A.. Charles, D., Levy, P., and Kass, E. H.: Birth weight and genital mycoplasmas in pregnancy, N. Engl. J. Med. 284: 167, 1971. 4. Braun. P .. Klein, J. 0., Lee, Y. H., Marcy. S. M., Klein, T. A., Charles, D., Levy, P., and Kass, E. H.: Methodologic investigations and prevalence of genital mycoplasmas in pregnancy, J. Infect. Dis. 121: 391, 1970. 5. de Louvois, J., Blades, M., Harrison, R. F., Hurley, R., and Stanley, V. C.: Frequency of mycoplasma in fertile and infertile couples, Lancet 2: 1073, 1974. 6. Tanner.]. M.. and Thomson, A.M.: Standards for bilth weight at gestation periods from 32-42 weeks, allowing for maternal height and weight. Arch. Dis. Child. 45: 566, 1970.
7. di Musto, J. C., Bohjalian, 0., and Millar, M.: Mycoplasma hominis type 1 infection and pregnancy, Obstet. Gynaecol. 41: 33, 1973. 8. Pease, P., Rogers, K. B., and Cole, B. C.: A cytopathogenic strain of Mycoplasma hominis type 1 isolated from the lungs of a stillborn infant, J. Path. Bact. 94: 460. 1967. 9. Jones, D. M.: Mycoplasma hominis in abortion. Br. Med. J. 1: 338, 1967. 10. Driscoll, S. G., Kundsin, R. B .. Horne, H. W., Jr., and Scott, J. M.: Infections and first trimester losses: Possible role of mycoplasmas, Fettil. Steril. 20: 1017, 1969. 11. Kundsin, R. B., Driscoll, S. G., and Ming. P. L.: Strain of mycoplasma associated with human reproductive failure, Science 157: 1573, 1967. 12. Kundsin, R. B .. and Driscoll, S. G.: Mycoplasmas and human reproductive failure, Surg. Gynecol. Obstet. 131: 89, 1970. 13. Harrison. R. F., deLouvois.J ., Blades, M., and Hurley. R.: Doxycycline treatment and human infertility. Lancet 1: 605, 1975.
