American Jam& of Obstetrics and Gynecology volume
Hydatidiform WALTER
B.
NIELS New
H. York,
number
3
JUNE
1,
1975
mole with coexistent fetus
JONES,
M.D.
LAUERSEN,
New
122
M.D.
York
Eight cases of hydatidiform mole with coexistent fetus are presented with special considerations of diagnosis and management. Although the incidence of this condition was one in 22,000 pregnancies, it is emphasized that the combination of a mole with a fetus should be included in the differential diagnosis of patients who have signs and symptoms of gestational trophoblastic disease in the presence of a fetus. Recommended treatment is immediate termination of the pregnancy. Appropn’ate follow-up with a sensitive and specific gonadotropin assay is required to differentiate minimal tumor activity from normal levels of pituitary luteiniring hormone. None of the patients in this series developed malignant
trophoblastic
neoplasia.
Table I. Obstetric statistics Hospital-Cornell University 1932 to 1973
HY D AT ID I F ORM M 0 LE iS a COInparatidy rare disease in the United States. The incidence most often quoted is 1 in 2,000 pregnancies.l The occurrence of a hydatidiform mole with a coexisting fetus is extremely rare, the incidence reported varying from 1: 10,000 to 1 : 100,000 pregnancies.‘-” The true occurrence is difficult to determine since only abortuses showing macroscopic abnormalities are submitted for histologic examination in some
Total pregnancies (deliveries and abortions) Abortions (including elective abortions) Trophoblastic disease Choriocarcinoma Malignant mole Intermediate mole Benign mole Hydatidiform mole and coexistent fetus
From the Department of Obstetrics and Gynecology, The New York Hospital-Cornell l.!niversity Medical College, and the Memorial Sloan-Kettering Cancer Center. Received Revised Accepted
for publication October November
Reprint requests: Sloan-Kettering New York, New
August
175,990 23,088 18 11 11 135 8
hospitals. Because of this, microscopic molar changes are not included in such reports. Although the presence of a coexistent fetus with a molar pregnancy has been considered a rarity, the observation that it can occur at all is important to the etiology of a hydatidiform mole. It is also important in regard to the differential diagnosis of
12, 1974.
17, 1974. 27, 1974. Dr. W. B. Jones, Memorial Cancer Center, 1275 York York 10021.
at The New York Medical Center,
Ave.,
267
11. Summary
Table
of patients
with mole and coexistent
Ape of Case NO.
__-
patient (yearr)
~
Parity
1 2 3
17 -.“‘{ 28
0 0 2
4 5 6 7 8
23 28 26 33 23
1 1 0 2 0
Mode of presenation
fetus Gestation (wk.) at termination
Delivery Uterine bleeding Uterine growth retardation Uterine bleeding Missed abortion Pre-eclampsia Uterine bleeding Uterine bleeding
Method of termination
40 14 26 19 34 20 “4 17
Delivery Hysterotomy Curetagc and chemotherapy Curettage Curettage Hysterotomy Curettage Curettage
.~
Fetal
.iex
Female Femal.? Undetermined Male Undetermined Male Undetermined Undetermined
cases of hydatidiform mole with coexistent fetus seen at the New York Hospital-Cornell Medical Center between 1932 and 1973. Special attention will be given to three patients who demonstrate the varied marmgement problems in these cases. Material
A
t
t
1
Fig. 1. A term placenta, weighing 1,020 grams, measuring 25 by 19 cm.; a marginal portion, approximately 25 per cent of the surface, consisted of numerous thin-walled, grapelike vesicles.
an undelivered molar pregnancy. The presence of a viable fetus with a molar placenta (without evidence of a twin pregnancy) argues against the theory that death of the embryo is the initiating event in the formation of a hydatidiform mole. The diagnosis of this condition prior to evacuation of the uterus is difficult if the only diagnostic methods used are those which depend on the absence of a fetus (absence of fetal heart tones, presence of skeletal parts on x-ray, etc.). The purpose of this report is to present eight
Between 1932 and 1973, there were 175,990 pregnancies cared for at the New York Lying-In HOSpital, of which 23,088 ended in abortion. During the same interval, there were 183 patients admitted with some form of gestational trophoblastic disease (Table I). The diagnoses in these 183 patients were : choriocarcinoma, 18 ; malignant mole, 11 ; intermediate mole, 11; benign mole, 135. There were eight patients in whom the hydatidiform mole was associated with a coexistent fetus. In this series the incidence of mole with coexistent fetus was 1 per 22,000 pregnancies, 1 per 2,875 abortions, and 1 per 20 molar pregnancies. Thus, 5 per cent of the molar pregnancies had an associated fetus. Of these eight cases, grossly identifiable molar changes were seen in six, while in the other two the diagnosis was made only with subsequent histologic examination. The cases are presented in Table II with respect to the patient’s age, parity, mode of presentation, weeks of gestation, method of termination of pregnancy, and fetal sex. The following case histories illustrate the association of a mole and coexistent fetus. Case Case
reports 1. A
17-year-old primigravida was followed in the clinic, where she had a normal antepartum course. She was admitted to the hospital in early labor and had a normal spontaneous delivery at term of a 2,W) gram
normal female infant with an Apgar score of !I to 10. The placenta was delivered spontaneously. Approximately
25 per
cent
of the
placenta
consisted
of a struc-
Volume Number
122 3
Hydatidiform
Fig. 2. Ultrasonography showing: (I) gestational sac of located fetal ethos; (2) the uterine cavity of approximately hydatidiform mole; (3) and (4) bilateral ovarian cysts.
mole
13 weeks’ gestation 16 weeks’ gestation
with
coexistent
fetus
269
with centrally with ethos of
Fig. 3. Termination by hysterotomy of a molar pregnancy with an associated fetus. The fetus inside the fetal membranes is presenting through the hysterotomy incision. Directly behind the fetus, a large amount of molar tissue can be observed. Large bilateral tbeca-lutein cysts are present, confirming the sonographic diagnosis illustrated in Fig. 2.
ture whit :h grossly appeared to be a hydatidiform mole. The plats ental weight was 1,020 grams, and it measured 25 by 19 cm. in diameter. The maternal surface of the placenta consisted of two distinct parts. A marginal portion, :amounting to 25 per cent of the surface, con&ted of numerous, thin-walled, grapelike cysts. The major pc jrtion of the placenta was of normal texture (Fig. 1). On microscopic examination, a term placenta with part :ial hydatidiform mole was described.
The patient was again followed in the antepa krtum clinic and had a spontaneous term delivery 11 m later of a 4,040 gram male infant. The placenta I was examined microscopically and found to be normal Case 2. A 23-year-old patient, gravida 2, pa ra 0, abortus 1, developed vaginal spotting in the fifth week of gestation; spotting, intermittent bright red blet :ding, and severe nausea occurred until admission to the ho spital at 14 weeks’ gestation to rule out a molar or twin preg-
Fig. 4. Gross tion
specimen showing a fetus and a large amount of hydatidiform
of 13 weeks’ mole.
gesta-
nancy. On physical examination, the fundus leas approximately 14 to 16 \veeks’ gestational size. The fetal heartbeat was not heard. A 24 hour urine collection for human chorionic gonadotropin (HCG) \vas markedly elevated (3 million 1.L. per 24 hours). .4 roentgenogram of the abdomen showed a large centrally located mass overlying the sacrum and no skeletal parts. A sonogram was ohtained which indicated the presence of a small fetus in an amniotic sac, a large amount of hydatidiform mole, and hilateral ovarian cysts (Fig. 2;. .4n abdominal hysterotomy \vas performed on the third day of adjunctive methotrexate therapy. The uterus was found to he approximately 20 weeks’ gestation in size (larger than indicated by the dates), and hoth ovaries rvere enlarged and cystic, approximately JO to 12 ~111. in diameter. When the uterine cavity was entered, a fetus in a sac \vas first delibrered, and this \vas followed hy a large amount of molar tissue (Fig. 3). Histopathologic analysis revealed a hydatidiform mole (800 grams; 0 1’ to 120 U. on the third day of a planned f+ve-d;!v coursr of adjunctive chemotherapy, treatment was discolltipul,r!. The peak of the SGOT elevation was 215 1.. IIn t il., fourth day after initiation of therapy. The patie!lt’:> pconald,x sonar at present does not involve any known hazards. In Case No. 2 bilateral thecalutein cysts were identified in addition to the mole and fetus. Transabdominal injection of contrast media is a relatively recent technique that allows early diagnosis with remarkable accuracy.!‘* I” There were no symptoms in these patients with coexistent fetuses which distinguished them from other patients with hydatidiform moles alone. Three of the eight patients had as their initial symptom uterine bleeding that progressed to abortion while another was thought to have a missed abortion. Toxemia prior to the twenty-fourth week of gestation is a rare complication of pregnancy, and, when
272
-[ones
04
it does occur, as a possibility. condition
Loversen
molar
as in
must
include
\,alue
of
pregnancy
When Case a
must
be
considered
a fetus is detected No.
mole
6 the and
a thorough
with
differential
diagnosis
coexistent
examination
of
this
fetus. the
The
afterbirth
is seen in Case No. 1 in which macroscopic changes were associated with a term placenta. It is emphasized that the products of all conceptions should be submitted for histologic evaluation so that microscopic molar changes can be accurately reported. Finally, a mole and coexistent fetus were demonstrated by sonography in Case No. 2, while in Case No. 3 the mole could be identified but the evidence for
the
patients
fetus
was
have
subsequently
inconclusive.
treatment
The chemotherapy
as
of a
Five had
normal
trophoblastic
primary
of
the
term
eight births.
disease
therapeutic
with
modality
continues to be one of the most rewarding aspects of gynecologic oncology. Since 1956, when Li and associates” reported the successful use of methotrexate
in
metastatic
gestational
trophoblastic
dis-
ease, many investigators have confirmed the efficacy of chemotherapy in both metastatic and nonmetastatir gestational trophoblastic disease.‘“-” It is emphasized here that the treatment of hydatidiform mole with a coexistent fetus is immediate termina-
REFERENCES
1. 2. 3. 4. 5. 6.
tion of the pregnancy. Hysterotom\ ii I rrei! illdicated, since, even when the uterus is e&t-cd, I!lust patients can be safely evacuated with o~vcoc~n followed by suction curettage or sharll I IIW~~:I~ Lewis” and Goldstein’!’ have dcmonstl-:llrti thz value of adjunctive chemotherapy wlcetl O~XT:I ;ion is required in the management. During I’olIcm -up, gonadotropin activity must be measurc,d &~LVI: 10 J level that can be accounted for by pituitary iutriniying hormone in order to detect persistcncct of dkease or malignant degeneration at the earlkst rim?. Sensitive radioimmunoassays and bioassays are essential for this purpose. We wish to thank Dr. John L. Lewis, Jr., Chief of the Gynecology Service, Memorial Sloan-Kettering Cancer Center, for his valuable suggestions and critical review of this work, and Dr. Elmer Kramer, Professor of Obstetrics and Gynecology and Clinical Professor of Pathology, Cornell University Medical College, for pathologic data included in this study. WC are grateful to Dr. Tholnas Steadman for his collaboration in the treatment of one of the patients and to Dr. Lajos I. VOII Micsky, Ikector of Ultra-Sound Laboratory, St. Luke’s Hospital, New York, New York, for the sonographic examination of one of the patients (Fig. 2).
10.
Hertig, A. T., and Sheldon, W. H.: AM. J. OBSTET. GYNECOL. 53: 1, 1947. Bowles, H. E.: AM. J. OBSTET. GYNECOL. 46: 154, 1943. Ruffolo, E. H.: Obstet. Gynecol. 8: 296, 1956. Beischer, N. A.: J. Obstet. Gynaecol. Br. Commonw. 68: 231, 1961. Hertia. A. T., and Edmonds. H. W.: Arch. Pathol. 30: 266, 1940. Park, W. W.: In Holland, J. F., and Hreshchyshyn, M.. editors: U.I.C.C. Monocraph. Berlin. 1967. vol. 3, Springer Verlag. Be&her, N. A.: Aust. N. Z. J. Obstet. Gynaecol. 6: 127, 1966. Donald, I.: In Greenhill, J. P., editor: Year Book of Obstetrics and Gynecology 1967-1968, Chicago, 1968, Year Book Medical Publishers, Inc. Torres, H., and Pelegrina, I. A.: AM. J. OBSTET. GYNECOL. 94: 936, 1966. -
-
I
11. 12. 13. 14. 15. 16.
17.
18. 19.
Zarou, D. M., Imbealu, Y., and Zarou, G. S.: Obstet. Gynecol. 35: 89, 1970. Li, M. C., Hertz, R., and Spencer, D. B.: Proc. Sot. EXP. Biol. Med. 93: 361. 1956. Hertz, R., Lewis, J. L.: Jr., and Lipsett, M. B.: AM. J. OBSTET.GYNECOL. 82:631,1961. Hammond, C. B., and Parker, R. T.: Obstet. Gynecol. 35: 132, 1970. Goldstein, D. P.: J. A. M. A. 220: 209, 1972. Jones, W. B., and Lewis, J. L., Jr.: AM. J. OBSTET. GYNECOL. 120: 14, 1974. Ross, G. T., Goldstein, D. P., Hertz, R., Lipsett, M. B., and Odell, W. D.: AM. J. OBSTET. GYNECOL. 93: 223, 1965. Brewer, J. I., Eckman, T. R., Dolkart, R. E., and Webster, A.: AM. J. OBSTET. GYNECOL. 109: 335, 1971. Lewis, J. L., Jr.: Med. Clin. North Am. 49: 371, 1969. Goldstein, D. P.: Obstet. Gynecol. 38: 817, 1971.
Hydatidiform WALTER
B.
NIELS New
H. York,
number
3
JUNE
1,
1975
mole with coexistent fetus
JONES,
M.D.
LAUERSEN,
New
122
M.D.
York
Eight cases of hydatidiform mole with coexistent fetus are presented with special considerations of diagnosis and management. Although the incidence of this condition was one in 22,000 pregnancies, it is emphasized that the combination of a mole with a fetus should be included in the differential diagnosis of patients who have signs and symptoms of gestational trophoblastic disease in the presence of a fetus. Recommended treatment is immediate termination of the pregnancy. Appropn’ate follow-up with a sensitive and specific gonadotropin assay is required to differentiate minimal tumor activity from normal levels of pituitary luteiniring hormone. None of the patients in this series developed malignant
trophoblastic
neoplasia.
Table I. Obstetric statistics Hospital-Cornell University 1932 to 1973
HY D AT ID I F ORM M 0 LE iS a COInparatidy rare disease in the United States. The incidence most often quoted is 1 in 2,000 pregnancies.l The occurrence of a hydatidiform mole with a coexisting fetus is extremely rare, the incidence reported varying from 1: 10,000 to 1 : 100,000 pregnancies.‘-” The true occurrence is difficult to determine since only abortuses showing macroscopic abnormalities are submitted for histologic examination in some
Total pregnancies (deliveries and abortions) Abortions (including elective abortions) Trophoblastic disease Choriocarcinoma Malignant mole Intermediate mole Benign mole Hydatidiform mole and coexistent fetus
From the Department of Obstetrics and Gynecology, The New York Hospital-Cornell l.!niversity Medical College, and the Memorial Sloan-Kettering Cancer Center. Received Revised Accepted
for publication October November
Reprint requests: Sloan-Kettering New York, New
August
175,990 23,088 18 11 11 135 8
hospitals. Because of this, microscopic molar changes are not included in such reports. Although the presence of a coexistent fetus with a molar pregnancy has been considered a rarity, the observation that it can occur at all is important to the etiology of a hydatidiform mole. It is also important in regard to the differential diagnosis of
12, 1974.
17, 1974. 27, 1974. Dr. W. B. Jones, Memorial Cancer Center, 1275 York York 10021.
at The New York Medical Center,
Ave.,
267
11. Summary
Table
of patients
with mole and coexistent
Ape of Case NO.
__-
patient (yearr)
~
Parity
1 2 3
17 -.“‘{ 28
0 0 2
4 5 6 7 8
23 28 26 33 23
1 1 0 2 0
Mode of presenation
fetus Gestation (wk.) at termination
Delivery Uterine bleeding Uterine growth retardation Uterine bleeding Missed abortion Pre-eclampsia Uterine bleeding Uterine bleeding
Method of termination
40 14 26 19 34 20 “4 17
Delivery Hysterotomy Curetagc and chemotherapy Curettage Curettage Hysterotomy Curettage Curettage
.~
Fetal
.iex
Female Femal.? Undetermined Male Undetermined Male Undetermined Undetermined
cases of hydatidiform mole with coexistent fetus seen at the New York Hospital-Cornell Medical Center between 1932 and 1973. Special attention will be given to three patients who demonstrate the varied marmgement problems in these cases. Material
A
t
t
1
Fig. 1. A term placenta, weighing 1,020 grams, measuring 25 by 19 cm.; a marginal portion, approximately 25 per cent of the surface, consisted of numerous thin-walled, grapelike vesicles.
an undelivered molar pregnancy. The presence of a viable fetus with a molar placenta (without evidence of a twin pregnancy) argues against the theory that death of the embryo is the initiating event in the formation of a hydatidiform mole. The diagnosis of this condition prior to evacuation of the uterus is difficult if the only diagnostic methods used are those which depend on the absence of a fetus (absence of fetal heart tones, presence of skeletal parts on x-ray, etc.). The purpose of this report is to present eight
Between 1932 and 1973, there were 175,990 pregnancies cared for at the New York Lying-In HOSpital, of which 23,088 ended in abortion. During the same interval, there were 183 patients admitted with some form of gestational trophoblastic disease (Table I). The diagnoses in these 183 patients were : choriocarcinoma, 18 ; malignant mole, 11 ; intermediate mole, 11; benign mole, 135. There were eight patients in whom the hydatidiform mole was associated with a coexistent fetus. In this series the incidence of mole with coexistent fetus was 1 per 22,000 pregnancies, 1 per 2,875 abortions, and 1 per 20 molar pregnancies. Thus, 5 per cent of the molar pregnancies had an associated fetus. Of these eight cases, grossly identifiable molar changes were seen in six, while in the other two the diagnosis was made only with subsequent histologic examination. The cases are presented in Table II with respect to the patient’s age, parity, mode of presentation, weeks of gestation, method of termination of pregnancy, and fetal sex. The following case histories illustrate the association of a mole and coexistent fetus. Case Case
reports 1. A
17-year-old primigravida was followed in the clinic, where she had a normal antepartum course. She was admitted to the hospital in early labor and had a normal spontaneous delivery at term of a 2,W) gram
normal female infant with an Apgar score of !I to 10. The placenta was delivered spontaneously. Approximately
25 per
cent
of the
placenta
consisted
of a struc-
Volume Number
122 3
Hydatidiform
Fig. 2. Ultrasonography showing: (I) gestational sac of located fetal ethos; (2) the uterine cavity of approximately hydatidiform mole; (3) and (4) bilateral ovarian cysts.
mole
13 weeks’ gestation 16 weeks’ gestation
with
coexistent
fetus
269
with centrally with ethos of
Fig. 3. Termination by hysterotomy of a molar pregnancy with an associated fetus. The fetus inside the fetal membranes is presenting through the hysterotomy incision. Directly behind the fetus, a large amount of molar tissue can be observed. Large bilateral tbeca-lutein cysts are present, confirming the sonographic diagnosis illustrated in Fig. 2.
ture whit :h grossly appeared to be a hydatidiform mole. The plats ental weight was 1,020 grams, and it measured 25 by 19 cm. in diameter. The maternal surface of the placenta consisted of two distinct parts. A marginal portion, :amounting to 25 per cent of the surface, con&ted of numerous, thin-walled, grapelike cysts. The major pc jrtion of the placenta was of normal texture (Fig. 1). On microscopic examination, a term placenta with part :ial hydatidiform mole was described.
The patient was again followed in the antepa krtum clinic and had a spontaneous term delivery 11 m later of a 4,040 gram male infant. The placenta I was examined microscopically and found to be normal Case 2. A 23-year-old patient, gravida 2, pa ra 0, abortus 1, developed vaginal spotting in the fifth week of gestation; spotting, intermittent bright red blet :ding, and severe nausea occurred until admission to the ho spital at 14 weeks’ gestation to rule out a molar or twin preg-
Fig. 4. Gross tion
specimen showing a fetus and a large amount of hydatidiform
of 13 weeks’ mole.
gesta-
nancy. On physical examination, the fundus leas approximately 14 to 16 \veeks’ gestational size. The fetal heartbeat was not heard. A 24 hour urine collection for human chorionic gonadotropin (HCG) \vas markedly elevated (3 million 1.L. per 24 hours). .4 roentgenogram of the abdomen showed a large centrally located mass overlying the sacrum and no skeletal parts. A sonogram was ohtained which indicated the presence of a small fetus in an amniotic sac, a large amount of hydatidiform mole, and hilateral ovarian cysts (Fig. 2;. .4n abdominal hysterotomy \vas performed on the third day of adjunctive methotrexate therapy. The uterus was found to he approximately 20 weeks’ gestation in size (larger than indicated by the dates), and hoth ovaries rvere enlarged and cystic, approximately JO to 12 ~111. in diameter. When the uterine cavity was entered, a fetus in a sac \vas first delibrered, and this \vas followed hy a large amount of molar tissue (Fig. 3). Histopathologic analysis revealed a hydatidiform mole (800 grams; 0 1’ to 120 U. on the third day of a planned f+ve-d;!v coursr of adjunctive chemotherapy, treatment was discolltipul,r!. The peak of the SGOT elevation was 215 1.. IIn t il., fourth day after initiation of therapy. The patie!lt’:> pconald,x sonar at present does not involve any known hazards. In Case No. 2 bilateral thecalutein cysts were identified in addition to the mole and fetus. Transabdominal injection of contrast media is a relatively recent technique that allows early diagnosis with remarkable accuracy.!‘* I” There were no symptoms in these patients with coexistent fetuses which distinguished them from other patients with hydatidiform moles alone. Three of the eight patients had as their initial symptom uterine bleeding that progressed to abortion while another was thought to have a missed abortion. Toxemia prior to the twenty-fourth week of gestation is a rare complication of pregnancy, and, when
272
-[ones
04
it does occur, as a possibility. condition
Loversen
molar
as in
must
include
\,alue
of
pregnancy
When Case a
must
be
considered
a fetus is detected No.
mole
6 the and
a thorough
with
differential
diagnosis
coexistent
examination
of
this
fetus. the
The
afterbirth
is seen in Case No. 1 in which macroscopic changes were associated with a term placenta. It is emphasized that the products of all conceptions should be submitted for histologic evaluation so that microscopic molar changes can be accurately reported. Finally, a mole and coexistent fetus were demonstrated by sonography in Case No. 2, while in Case No. 3 the mole could be identified but the evidence for
the
patients
fetus
was
have
subsequently
inconclusive.
treatment
The chemotherapy
as
of a
Five had
normal
trophoblastic
primary
of
the
term
eight births.
disease
therapeutic
with
modality
continues to be one of the most rewarding aspects of gynecologic oncology. Since 1956, when Li and associates” reported the successful use of methotrexate
in
metastatic
gestational
trophoblastic
dis-
ease, many investigators have confirmed the efficacy of chemotherapy in both metastatic and nonmetastatir gestational trophoblastic disease.‘“-” It is emphasized here that the treatment of hydatidiform mole with a coexistent fetus is immediate termina-
REFERENCES
1. 2. 3. 4. 5. 6.
tion of the pregnancy. Hysterotom\ ii I rrei! illdicated, since, even when the uterus is e&t-cd, I!lust patients can be safely evacuated with o~vcoc~n followed by suction curettage or sharll I IIW~~:I~ Lewis” and Goldstein’!’ have dcmonstl-:llrti thz value of adjunctive chemotherapy wlcetl O~XT:I ;ion is required in the management. During I’olIcm -up, gonadotropin activity must be measurc,d &~LVI: 10 J level that can be accounted for by pituitary iutriniying hormone in order to detect persistcncct of dkease or malignant degeneration at the earlkst rim?. Sensitive radioimmunoassays and bioassays are essential for this purpose. We wish to thank Dr. John L. Lewis, Jr., Chief of the Gynecology Service, Memorial Sloan-Kettering Cancer Center, for his valuable suggestions and critical review of this work, and Dr. Elmer Kramer, Professor of Obstetrics and Gynecology and Clinical Professor of Pathology, Cornell University Medical College, for pathologic data included in this study. WC are grateful to Dr. Tholnas Steadman for his collaboration in the treatment of one of the patients and to Dr. Lajos I. VOII Micsky, Ikector of Ultra-Sound Laboratory, St. Luke’s Hospital, New York, New York, for the sonographic examination of one of the patients (Fig. 2).
10.
Hertig, A. T., and Sheldon, W. H.: AM. J. OBSTET. GYNECOL. 53: 1, 1947. Bowles, H. E.: AM. J. OBSTET. GYNECOL. 46: 154, 1943. Ruffolo, E. H.: Obstet. Gynecol. 8: 296, 1956. Beischer, N. A.: J. Obstet. Gynaecol. Br. Commonw. 68: 231, 1961. Hertia. A. T., and Edmonds. H. W.: Arch. Pathol. 30: 266, 1940. Park, W. W.: In Holland, J. F., and Hreshchyshyn, M.. editors: U.I.C.C. Monocraph. Berlin. 1967. vol. 3, Springer Verlag. Be&her, N. A.: Aust. N. Z. J. Obstet. Gynaecol. 6: 127, 1966. Donald, I.: In Greenhill, J. P., editor: Year Book of Obstetrics and Gynecology 1967-1968, Chicago, 1968, Year Book Medical Publishers, Inc. Torres, H., and Pelegrina, I. A.: AM. J. OBSTET. GYNECOL. 94: 936, 1966. -
-
I
11. 12. 13. 14. 15. 16.
17.
18. 19.
Zarou, D. M., Imbealu, Y., and Zarou, G. S.: Obstet. Gynecol. 35: 89, 1970. Li, M. C., Hertz, R., and Spencer, D. B.: Proc. Sot. EXP. Biol. Med. 93: 361. 1956. Hertz, R., Lewis, J. L.: Jr., and Lipsett, M. B.: AM. J. OBSTET.GYNECOL. 82:631,1961. Hammond, C. B., and Parker, R. T.: Obstet. Gynecol. 35: 132, 1970. Goldstein, D. P.: J. A. M. A. 220: 209, 1972. Jones, W. B., and Lewis, J. L., Jr.: AM. J. OBSTET. GYNECOL. 120: 14, 1974. Ross, G. T., Goldstein, D. P., Hertz, R., Lipsett, M. B., and Odell, W. D.: AM. J. OBSTET. GYNECOL. 93: 223, 1965. Brewer, J. I., Eckman, T. R., Dolkart, R. E., and Webster, A.: AM. J. OBSTET. GYNECOL. 109: 335, 1971. Lewis, J. L., Jr.: Med. Clin. North Am. 49: 371, 1969. Goldstein, D. P.: Obstet. Gynecol. 38: 817, 1971.
