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The effect of cone biopsy on subsequent pregnancy outcome
GYNECOLOGIC
ONCOLOGY
6, 1-6 (1978)
The Effect of Cone Biopsy on Subsequent Pregnancy Outcome N. H. LEE, MBBS, Department Columbia,
FRCS(C)’
of Obstetrics and Gynaecology, Faculty of Medicine, University Vancouver General Hospital, Vancouver, British Columbia, Canada
of British V5.Z IM9
Received March IO, 1977 One hundred and thirty-one pregnancies occurring in 97 patients following cone biopsy were reviewed. Excluding therapeutic abortions, 27.1% of the remaining pregnancies terminated in spontaneous abortions and 11.3% in labor prior to 36 weeks. However, because of other abnormal preceding factors in many of these cases, in only a few could cone biopsy be implicated as a likely etiological factor. The majority of viable pregnancies and labors were uncomplicated. Nonetheless, it would seem advisable to minimize the risk of complications with the use of colposcopy and a “shallow” cone or by the use of cryosurgery in the treatment of preclinical carcinoma of the cervix.
The effects of cone biopsy of the cervix on subsequent pregnancy outcome have been much discussed, the majority of reports suggesting few complications. Kullander et al. 111, Green 123, MacVicar et al. 131, and Fettig and Kuhn 143concluded that there were no major adverse effects upon fertility, the incidence of spontaneous abortion, or of premature labor. Soiva and Laine IS], however, felt that there might be an increased predisposition to abortion and premature labor because of cervical incompetence. Burghardt [6] found that the duration of labor was increased as compared with the average in his clinic and that caesarean section was performed in 11.1% of cases because of cervical dystocia. However, Fettig and Kuhn [4] noted a marked reduction in the duration of labor compared with their normal patients. MacVicar et al. [3] and McLaren [7] reported cases of caesarean section because of cervical dystocia, and Green 121 reported cervical lacerations following delivery. In the British Columbia population, Benedet et al. 181have recently reported a marked increase in the number of young women presenting with preclinical carcinoma of the cervix. They discuss the use of colposcopy as an adjunct to cytology screening programs and the possibility of its use in reducing the number of conizations performed. Townsend and Ostergard [9] and Kaufman et al. [IO] advocate the use of cryosurgery rather than conization for treatment of preinvasive cervical carcinoma in selected patients. However, there continues to be a ’ Reprint requests to Dr. N. H. Lee, Department of Obstetrics and Gynaecology, Willow Pavilion, Vancouver General Hospital, Vancouver, British Columbia, Canada VSZ 1M9.
0090-8258/78/0061-0001$01.00/0 Copyright @ 1978 by Academic Press, Inc. All rights of reproduction in any form reserved.
2
N.
H.
LEE
large number of women in whom cone biopsy is performed for either definitive diagnosis or treatment, or both, of this disease. Because of the increasing number of young women likely to be subjected to cone biopsy, it remains important to investigate the effect of the procedure upon fertility and future pregnancy. MATERIALS
AND METHODS
The records of 97 patients who had had cone biopsies performed between 1958 and 1973, and subsequently had pregnancies terminating in the same institution, were reviewed. Data on 131 pregnancies were thus collected, excluding those where cone biopsy was performed during the pregnancy itself. An attempt to assess fertility after the procedure was not made, pregnancy outcome alone being the purpose of this study. All patients had cone biopsies prior to the introduction of colposcopy at our center. The operations were performed by several surgeons with resulting variations in the amount of tissue removed. All conization specimens were classified the definition of an adequate cone being as either “adequate” or “inadequate,” “one that was complete, i.e., not torn and not different in any part, and that was 2 cm in diameter and 2 cm in length up the endocervical canal and including the squamocolumnar junction.” Therefore, all patients had cones that included a significant amount of the endocervical canal, it being the policy of our center, during the time of this review, to attempt to remove cones fulfilling the above criteria and not to perform a “ring” type of biopsy. Fractional curettage was performed in all cases and, in the majority, the Sturmdorf method was used to repair the cervix. RESULTS
Ninety-two of the patients were aged between 20 and 35 years, four being younger than 20 years and one being older than 35 years. Twenty-four of the patients had their first pregnancy following cone biopsy, 25 had had one prior pregnancy, and the remaining 48 patients had had two or more pregnancies prior to the cone. The time interval between the cone biopsy and the first conception following the cone is shown in Table 1. Hence, 49.5% of the patients conceived with 1 year and 74.2% of the total within 2 years. It appears, therefore, that, when pregnancy occurs following cone biopsy, it does not normally follow a long period of infertility. The outcome of the I3 1 pregnancies following cone biopsy is shown in Table 2. TABLE INTERVAL
Interval Number
(years) of patients
BETWEEN
o-1 48
CONE
I Bropsy 1-2 24
AND
CONCEPTION
2-4 15
4-6 8
6-8 2
CONE BIOPSY AND PREGNANCY TABLE PREGNANCY
OUTCOME
3
OUTCOME
2
FOLLOWING
CONE
BIOPSY
Number of pregnancies
Percentage of total pregnancies (%o)
23 6
17.5 4.6
Viable pregnancies < 32 Weeks 32-36 Weeks > 36 Weeks Therapeutic abortions Criminal abortion
3 9 65 24
2.3 6.9 49.6 18.3 0.8
Total
131
Pregnancy outcome Spontaneous abortions 6- I2 Weeks 13-20 Weeks
1
100.0
Spontaneous Abortion Twenty-four patients had 29 spontaneous abortions. Excluding pregnancies terminated as therapeutic abortions, the spontaneous abortion rate was 27.1%. Of these 24 patients, 10 had no further pregnancies and eight subsequently had normal pregnancies. Of the remaining six, one had a placenta previa, one had a premature labor at 28 weeks, one was treated with prolonged bed rest following the discovery of an effaced cervix at 30 weeks, and three were treated with cervical circlage because of a prior midtrimester spontaneous abortion postcone. Viable Pregnancies The gestational ages of the 77 pregnancies reaching viability are shown in Table 3. Sixty (77.9%) of these terminated in vaginal delivery and 17 (22.1%) in caesarean section. Length of labor for the former group is shown in Table 4. Three of the 17 caesarean sections were performed because of the failure of a “fibrotic” cervix to dilate, the remainder being elective or for other obstetric reasons considered unrelated to cone biopsy. TABLE LENGTH
Gestation (weeks)
3
OF GESTATION
Number of pregnancies
24-32 32-36
3 9
36-40 40 +
50 15
Percentage of viable pregnancies (%) 15.6
I
84.4
N. H. LEE
4
TABLE DURATION
Length of labor U-4
4
OF LABOR
Primigravida
Multigravida
O-6 6-12 12-18 18-24
7 11 2 I
28 9 2 -
Total
21
39
Four patients required repair of cervical lacerations following delivery, two of whom had had forceps deliveries. One patient, having a spontaneous delivery, had a severe tear extending through the cul-de-sac and into the posterior uterine wall. Perinatal Outcome
All viable pregnancies resulted in livebirths, there being one set of twins. One neonatal death of a 28-week premature infant occurred. Two other premature infants had respiratory distress syndrome but recovered. Excluding the twins, of the remaining 76 babies, 11 (14.5%) weighed 2500 g or less at birth (Table 5). Cervical Incompetence
Cervical incompetence was diagnosed clinically in five patients following the finding of effacement or dilatation, or both, of the cervix during pregnancy. One patient was managed with bed rest for 10 weeks and the remainder had Shirodkar sutures inserted between the sixteenth and thirtieth week of pregnancy. Of these five patients, one had had a prior premature labor and another had had a therapeutic abortion following cone biopsy. Three further patients were suspected of having cervical incompetence following a postcone midtrimester spontaneous abortion, although none were investigated following the loss. Each subsequently had two successful pregnancies, all of which were managed with cervical circlage. One of these patients had had two self-induced abortions prior to cone biopsy.
TABLE BIRTH
5
WEIGHT
Birth weight (9)
Postcone pregnancies (%)
Total pregnancies, 1958-1973” (%I
2500 or under over 2500
I l-14.5 65-85.5
7.7 92.3
@At Vancouver General Hospital.
CONE BIOPSY AND PREGNANCY
5
OUTCOME
It is possible that cervical incompetence was a contributing factor to the 11 labors resulting in babies of 2500 g or less. However, in none of these patients had the diagnosis been made prior to the labor. Five of these patients had had therapeutic abortions or premature labors prior to their cone biopsy, obscuring the significance of this procedure in predisposing to premature labor. In regard to spontaneous abortion, one would suspect that cone biopsy may predispose to midtrimester loss. Of the six such patients in this group, one had had two self-induced abortions precone and another had had two spontaneous abortions, again confusing the etiological significance of the cone biopsy. “Adequacy”
of Cone
Adequacy, as defined above, was assessed in 68 cases, excluding those where therapeutic abortion alone followed cone biopsy. The cone was adequate in 36 patients (52.9%) and inadequate in 32 (47.1%). It is likely that there was a tendency to remove smaller cones in women anticipating further families as, in a previous study of cone biopsy [ 11],7 1% of 1008 cones were considered adequate. In Table 6, adequacy is related to pregnancy outcome. DISCUSSION
Excluding therapeutic and criminal abortions, 106 pregnancies following cone biopsy were reviewed. The incidence of spontaneous abortion of 27.1% appears high, 15% being a widely accepted rate in the general population. However, the majority of these patients had either normal or no subsequent pregnancies and, in the remainder, the etiological significance of cone biopsy was often confused by other potential predisposing factors. Of greater significance was the 14.5% incidence of viable infants weighing 2500 g or less, as compared to 7.7% of our overall obstetric population in the same time period. It is likely that premature labor in some patients was prevented, seven having 11 pregnancies in which Shirodkar procedures were performed, 10 of these proceeding uneventfully to term. However, the majority of viable pregnancies resulted in livebirths after 36 weeks of gestation. One neonatal death occurred in the entire group, this being in a premature infant. Duration of labor did not appear to be significantly affected by cone biopsy, but cervical dystocia, necessitating caesarean section in three patients, was a complication likely resulting from cone biopsy. Although the size of the cone appears to
TABLE PREGNANCY
OUTCOME
6
AND “ADEQUACY”
Spontaneous abortion Adequacy Adequate Inadequate
First trimester 11 I
Second trimester
Premature labor
3 2
3 5
Full-term pregnancies 26 16
OF CONE
Caesarean sectioncervical dystocia I 1
Cervical trauma 1 3
Shirodkar suture 5 4
6
N. H. LEE
affect the immediate complication rate of cone biopsy [ 111, it could not be shown to influence pregnancy outcome in this group of patients. Hence, although the majority of viable pregnancies proceeded to term uneventfully, there was an increased incidence of infants weighing 2500 g or less. Some of these patients had predisposing factors other than cone biopsy which may have been significant in the causation of premature labor. However, it is advisable to follow all postcone pregnancies carefully to detect early signs of cervical incompetence, in order that treatment can be instituted in an attempt to prevent spontaneous abortion or premature labor. With the availability of colposcopy, therapeutic cone biopsy may be performed by removing tissue more superficially, provided the whole lesion can be visualized, with minimal risk of interfering with the internal cervical OS. The need for cone biopsy may be prevented entirely in many cases with the increasing use of colposcopy through the identification and treatment of those patients with small foci of preinvasive neoplasia and the following of them closely with cytology and colposcopy. The increasing use of cryosurgical techniques in the treatment of preclinical carcinoma may reduce the number of cones performed. It is hoped that, in these ways, complications of pregnancy due to cone biopsy may be avoided. REFERENCES I. Kullander, S., and Sjoberg, N. Treatment of carcinoma in situ of the cervix uteri by conization: A five year follow-up, Acta Obstet. Gynecol. Stand. 50, 153-157 (1971). 2. Green, G. H. Pregnancy following cervical carcinoma in situ: A review of 60 cases, J. Ohsret. Gynaecol. Brit. Commonw. 73, 897-902 (1966). 3. MacVicar, J., and Willocks, J. The effect of diathermy conization of the cervix on subsequent fertility, pregnancy and delivery, J. Obstet. Gynaecol. Brit. Commonw. 75, 355-356 (1968). 4. Fettig, O., and Kuhn, C. Konzeptionshauhgkeit, Schwangerschafts-und Geburtsverlauf nach zervix konisation, Geburtsh. Frauenheilk. 23, 517-527 (1963). 5. Soiva, K., and Laine, J. Pregnancy and cervical carcinoma in situ, Ann. Chir. Gynaecol. Fenn. 57, 131-134 (1%8). 6. Burghardt, E. Graviditaten nach Ringbiopsien, Konisationen und Portioamputationen, Geburtsh. Frauenheilk. 21, 225-236 (1961). 7. McLaren, H. C. Conservative management of cervical pre-cancer, J. Obstet. Gynaecol. Brit. Commonw. 74, 487-492 (1967). 8. Benedet, J. L., Boyes, D. A., Nichols, T. M., and Millner, A. Colposcopic evaluation of patients with abnormal cervical cytology, Brit. J. Obstet. Gynaecol. 83, 177-182 (1976). 9. Townsend, D. E., and Ostergard, D. R. Cryocauterization for preinvasive cervical neoplasia, J. Reprod. Med. 6, 55-59 (1971). IO. Kaufman, R. H., Strama, T., Norton, P. K., and Conner, J. S. Cryosurgical treatment of cervical intraepithelial neoplasia, Obstet. Gynecol. 42, 881 (1973). I I. Claman, A. D., and Lee, N. H. Factors that relate to complications of cone biopsy. Amer. J. Obstet. Gynecol. 120, 124-128 (1974).
ONCOLOGY
6, 1-6 (1978)
The Effect of Cone Biopsy on Subsequent Pregnancy Outcome N. H. LEE, MBBS, Department Columbia,
FRCS(C)’
of Obstetrics and Gynaecology, Faculty of Medicine, University Vancouver General Hospital, Vancouver, British Columbia, Canada
of British V5.Z IM9
Received March IO, 1977 One hundred and thirty-one pregnancies occurring in 97 patients following cone biopsy were reviewed. Excluding therapeutic abortions, 27.1% of the remaining pregnancies terminated in spontaneous abortions and 11.3% in labor prior to 36 weeks. However, because of other abnormal preceding factors in many of these cases, in only a few could cone biopsy be implicated as a likely etiological factor. The majority of viable pregnancies and labors were uncomplicated. Nonetheless, it would seem advisable to minimize the risk of complications with the use of colposcopy and a “shallow” cone or by the use of cryosurgery in the treatment of preclinical carcinoma of the cervix.
The effects of cone biopsy of the cervix on subsequent pregnancy outcome have been much discussed, the majority of reports suggesting few complications. Kullander et al. 111, Green 123, MacVicar et al. 131, and Fettig and Kuhn 143concluded that there were no major adverse effects upon fertility, the incidence of spontaneous abortion, or of premature labor. Soiva and Laine IS], however, felt that there might be an increased predisposition to abortion and premature labor because of cervical incompetence. Burghardt [6] found that the duration of labor was increased as compared with the average in his clinic and that caesarean section was performed in 11.1% of cases because of cervical dystocia. However, Fettig and Kuhn [4] noted a marked reduction in the duration of labor compared with their normal patients. MacVicar et al. [3] and McLaren [7] reported cases of caesarean section because of cervical dystocia, and Green 121 reported cervical lacerations following delivery. In the British Columbia population, Benedet et al. 181have recently reported a marked increase in the number of young women presenting with preclinical carcinoma of the cervix. They discuss the use of colposcopy as an adjunct to cytology screening programs and the possibility of its use in reducing the number of conizations performed. Townsend and Ostergard [9] and Kaufman et al. [IO] advocate the use of cryosurgery rather than conization for treatment of preinvasive cervical carcinoma in selected patients. However, there continues to be a ’ Reprint requests to Dr. N. H. Lee, Department of Obstetrics and Gynaecology, Willow Pavilion, Vancouver General Hospital, Vancouver, British Columbia, Canada VSZ 1M9.
0090-8258/78/0061-0001$01.00/0 Copyright @ 1978 by Academic Press, Inc. All rights of reproduction in any form reserved.
2
N.
H.
LEE
large number of women in whom cone biopsy is performed for either definitive diagnosis or treatment, or both, of this disease. Because of the increasing number of young women likely to be subjected to cone biopsy, it remains important to investigate the effect of the procedure upon fertility and future pregnancy. MATERIALS
AND METHODS
The records of 97 patients who had had cone biopsies performed between 1958 and 1973, and subsequently had pregnancies terminating in the same institution, were reviewed. Data on 131 pregnancies were thus collected, excluding those where cone biopsy was performed during the pregnancy itself. An attempt to assess fertility after the procedure was not made, pregnancy outcome alone being the purpose of this study. All patients had cone biopsies prior to the introduction of colposcopy at our center. The operations were performed by several surgeons with resulting variations in the amount of tissue removed. All conization specimens were classified the definition of an adequate cone being as either “adequate” or “inadequate,” “one that was complete, i.e., not torn and not different in any part, and that was 2 cm in diameter and 2 cm in length up the endocervical canal and including the squamocolumnar junction.” Therefore, all patients had cones that included a significant amount of the endocervical canal, it being the policy of our center, during the time of this review, to attempt to remove cones fulfilling the above criteria and not to perform a “ring” type of biopsy. Fractional curettage was performed in all cases and, in the majority, the Sturmdorf method was used to repair the cervix. RESULTS
Ninety-two of the patients were aged between 20 and 35 years, four being younger than 20 years and one being older than 35 years. Twenty-four of the patients had their first pregnancy following cone biopsy, 25 had had one prior pregnancy, and the remaining 48 patients had had two or more pregnancies prior to the cone. The time interval between the cone biopsy and the first conception following the cone is shown in Table 1. Hence, 49.5% of the patients conceived with 1 year and 74.2% of the total within 2 years. It appears, therefore, that, when pregnancy occurs following cone biopsy, it does not normally follow a long period of infertility. The outcome of the I3 1 pregnancies following cone biopsy is shown in Table 2. TABLE INTERVAL
Interval Number
(years) of patients
BETWEEN
o-1 48
CONE
I Bropsy 1-2 24
AND
CONCEPTION
2-4 15
4-6 8
6-8 2
CONE BIOPSY AND PREGNANCY TABLE PREGNANCY
OUTCOME
3
OUTCOME
2
FOLLOWING
CONE
BIOPSY
Number of pregnancies
Percentage of total pregnancies (%o)
23 6
17.5 4.6
Viable pregnancies < 32 Weeks 32-36 Weeks > 36 Weeks Therapeutic abortions Criminal abortion
3 9 65 24
2.3 6.9 49.6 18.3 0.8
Total
131
Pregnancy outcome Spontaneous abortions 6- I2 Weeks 13-20 Weeks
1
100.0
Spontaneous Abortion Twenty-four patients had 29 spontaneous abortions. Excluding pregnancies terminated as therapeutic abortions, the spontaneous abortion rate was 27.1%. Of these 24 patients, 10 had no further pregnancies and eight subsequently had normal pregnancies. Of the remaining six, one had a placenta previa, one had a premature labor at 28 weeks, one was treated with prolonged bed rest following the discovery of an effaced cervix at 30 weeks, and three were treated with cervical circlage because of a prior midtrimester spontaneous abortion postcone. Viable Pregnancies The gestational ages of the 77 pregnancies reaching viability are shown in Table 3. Sixty (77.9%) of these terminated in vaginal delivery and 17 (22.1%) in caesarean section. Length of labor for the former group is shown in Table 4. Three of the 17 caesarean sections were performed because of the failure of a “fibrotic” cervix to dilate, the remainder being elective or for other obstetric reasons considered unrelated to cone biopsy. TABLE LENGTH
Gestation (weeks)
3
OF GESTATION
Number of pregnancies
24-32 32-36
3 9
36-40 40 +
50 15
Percentage of viable pregnancies (%) 15.6
I
84.4
N. H. LEE
4
TABLE DURATION
Length of labor U-4
4
OF LABOR
Primigravida
Multigravida
O-6 6-12 12-18 18-24
7 11 2 I
28 9 2 -
Total
21
39
Four patients required repair of cervical lacerations following delivery, two of whom had had forceps deliveries. One patient, having a spontaneous delivery, had a severe tear extending through the cul-de-sac and into the posterior uterine wall. Perinatal Outcome
All viable pregnancies resulted in livebirths, there being one set of twins. One neonatal death of a 28-week premature infant occurred. Two other premature infants had respiratory distress syndrome but recovered. Excluding the twins, of the remaining 76 babies, 11 (14.5%) weighed 2500 g or less at birth (Table 5). Cervical Incompetence
Cervical incompetence was diagnosed clinically in five patients following the finding of effacement or dilatation, or both, of the cervix during pregnancy. One patient was managed with bed rest for 10 weeks and the remainder had Shirodkar sutures inserted between the sixteenth and thirtieth week of pregnancy. Of these five patients, one had had a prior premature labor and another had had a therapeutic abortion following cone biopsy. Three further patients were suspected of having cervical incompetence following a postcone midtrimester spontaneous abortion, although none were investigated following the loss. Each subsequently had two successful pregnancies, all of which were managed with cervical circlage. One of these patients had had two self-induced abortions prior to cone biopsy.
TABLE BIRTH
5
WEIGHT
Birth weight (9)
Postcone pregnancies (%)
Total pregnancies, 1958-1973” (%I
2500 or under over 2500
I l-14.5 65-85.5
7.7 92.3
@At Vancouver General Hospital.
CONE BIOPSY AND PREGNANCY
5
OUTCOME
It is possible that cervical incompetence was a contributing factor to the 11 labors resulting in babies of 2500 g or less. However, in none of these patients had the diagnosis been made prior to the labor. Five of these patients had had therapeutic abortions or premature labors prior to their cone biopsy, obscuring the significance of this procedure in predisposing to premature labor. In regard to spontaneous abortion, one would suspect that cone biopsy may predispose to midtrimester loss. Of the six such patients in this group, one had had two self-induced abortions precone and another had had two spontaneous abortions, again confusing the etiological significance of the cone biopsy. “Adequacy”
of Cone
Adequacy, as defined above, was assessed in 68 cases, excluding those where therapeutic abortion alone followed cone biopsy. The cone was adequate in 36 patients (52.9%) and inadequate in 32 (47.1%). It is likely that there was a tendency to remove smaller cones in women anticipating further families as, in a previous study of cone biopsy [ 11],7 1% of 1008 cones were considered adequate. In Table 6, adequacy is related to pregnancy outcome. DISCUSSION
Excluding therapeutic and criminal abortions, 106 pregnancies following cone biopsy were reviewed. The incidence of spontaneous abortion of 27.1% appears high, 15% being a widely accepted rate in the general population. However, the majority of these patients had either normal or no subsequent pregnancies and, in the remainder, the etiological significance of cone biopsy was often confused by other potential predisposing factors. Of greater significance was the 14.5% incidence of viable infants weighing 2500 g or less, as compared to 7.7% of our overall obstetric population in the same time period. It is likely that premature labor in some patients was prevented, seven having 11 pregnancies in which Shirodkar procedures were performed, 10 of these proceeding uneventfully to term. However, the majority of viable pregnancies resulted in livebirths after 36 weeks of gestation. One neonatal death occurred in the entire group, this being in a premature infant. Duration of labor did not appear to be significantly affected by cone biopsy, but cervical dystocia, necessitating caesarean section in three patients, was a complication likely resulting from cone biopsy. Although the size of the cone appears to
TABLE PREGNANCY
OUTCOME
6
AND “ADEQUACY”
Spontaneous abortion Adequacy Adequate Inadequate
First trimester 11 I
Second trimester
Premature labor
3 2
3 5
Full-term pregnancies 26 16
OF CONE
Caesarean sectioncervical dystocia I 1
Cervical trauma 1 3
Shirodkar suture 5 4
6
N. H. LEE
affect the immediate complication rate of cone biopsy [ 111, it could not be shown to influence pregnancy outcome in this group of patients. Hence, although the majority of viable pregnancies proceeded to term uneventfully, there was an increased incidence of infants weighing 2500 g or less. Some of these patients had predisposing factors other than cone biopsy which may have been significant in the causation of premature labor. However, it is advisable to follow all postcone pregnancies carefully to detect early signs of cervical incompetence, in order that treatment can be instituted in an attempt to prevent spontaneous abortion or premature labor. With the availability of colposcopy, therapeutic cone biopsy may be performed by removing tissue more superficially, provided the whole lesion can be visualized, with minimal risk of interfering with the internal cervical OS. The need for cone biopsy may be prevented entirely in many cases with the increasing use of colposcopy through the identification and treatment of those patients with small foci of preinvasive neoplasia and the following of them closely with cytology and colposcopy. The increasing use of cryosurgical techniques in the treatment of preclinical carcinoma may reduce the number of cones performed. It is hoped that, in these ways, complications of pregnancy due to cone biopsy may be avoided. REFERENCES I. Kullander, S., and Sjoberg, N. Treatment of carcinoma in situ of the cervix uteri by conization: A five year follow-up, Acta Obstet. Gynecol. Stand. 50, 153-157 (1971). 2. Green, G. H. Pregnancy following cervical carcinoma in situ: A review of 60 cases, J. Ohsret. Gynaecol. Brit. Commonw. 73, 897-902 (1966). 3. MacVicar, J., and Willocks, J. The effect of diathermy conization of the cervix on subsequent fertility, pregnancy and delivery, J. Obstet. Gynaecol. Brit. Commonw. 75, 355-356 (1968). 4. Fettig, O., and Kuhn, C. Konzeptionshauhgkeit, Schwangerschafts-und Geburtsverlauf nach zervix konisation, Geburtsh. Frauenheilk. 23, 517-527 (1963). 5. Soiva, K., and Laine, J. Pregnancy and cervical carcinoma in situ, Ann. Chir. Gynaecol. Fenn. 57, 131-134 (1%8). 6. Burghardt, E. Graviditaten nach Ringbiopsien, Konisationen und Portioamputationen, Geburtsh. Frauenheilk. 21, 225-236 (1961). 7. McLaren, H. C. Conservative management of cervical pre-cancer, J. Obstet. Gynaecol. Brit. Commonw. 74, 487-492 (1967). 8. Benedet, J. L., Boyes, D. A., Nichols, T. M., and Millner, A. Colposcopic evaluation of patients with abnormal cervical cytology, Brit. J. Obstet. Gynaecol. 83, 177-182 (1976). 9. Townsend, D. E., and Ostergard, D. R. Cryocauterization for preinvasive cervical neoplasia, J. Reprod. Med. 6, 55-59 (1971). IO. Kaufman, R. H., Strama, T., Norton, P. K., and Conner, J. S. Cryosurgical treatment of cervical intraepithelial neoplasia, Obstet. Gynecol. 42, 881 (1973). I I. Claman, A. D., and Lee, N. H. Factors that relate to complications of cone biopsy. Amer. J. Obstet. Gynecol. 120, 124-128 (1974).