- Email: [email protected]
Combined intrauterine and tubal pregnancy after in vitro fertilization and embryo transfer
Int. J. Gynecol. Obstet., 1990,33: 359-363 International Federation of Gynecology and Obstetrics
359
Combined intrauterine and tubal fertilization and embryo transfer H. Tani, K. Oda, K. Schichiri,
0. Arakawa
pregnancy
after in vitro
and Y. Sato
Department of Obstetrics and Gynecology, Niigata University, School of Medicine, I Asahimachi Dori, Niigata (Japan) (Received July 14th. 1989) (Revised and accepted September 21st, 1989)
Abstract
A case of combined intrauterine and tubal pregnancy after in vitro fertilization and embryo transfer is reported. As soon as the diagnosis was made at 9 weeks gestation, the fetal heart movement of the tubal pregnancy disappeared, and the patient was managed without surgery throughout the pregnancy course. After an infant was delivered, a right salpingectomy was performed and the diagnosis was histologically confirmed. Risk factors and treatments of combined pregnancy are discussed. Keywords: Combined (heterotopic) nancy; IVF-ET; Ectopic pregnancy.
preg-
Introduction
The techniques of in vitro fertilization and embryo transfer (IVF-ET) have been widely used as a treatment for infertility. However, some abnormal results have been reported; for example, ectopic pregnancy and multiple gestation. The first pregnancy after IVF-ET was a tubal pregnancy [14]. Since then, some reports have drawn attention to this possibility [2]. Combined intrauterine and tubal pregnancy, one of the rare conditions of ectopic 0020-7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
pregnancy, occurs in approximately one in 30,000 pregnancies [3]. We describe a case of a combined intrauterine and tubal pregnancy after IVF-ET and review some reported cases. Case report
The patient was a 25year-old woman with primary sterility. Bilateral tubal occlusion was suspected by hysterosalpingography. Laparoscopic examination revealed normal patency of the bilateral oviduct, but bilateral severe perifimbrial adhesions were found. The patient underwent laparoscopic fimbriolysis at the same time. Pregnancy failed to occur after 12 months observation and IVFET was considered. Ovarian hyperstimulation was achieved with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG). On day 13, eight oocytes were collected transvaginally by ultrasound, and were incubated and inseminated. Eighteen hours after sperm addition, normal fertilization of four oocytes was confirmed. Forty-eight hours after oocyte retrieval, four embroys were transferred in 15 ~1 of medium into the uterine cavity. At this time, the sounding of the cervix was needed because it was difficult to insert the ET catheter, and slight bleeding occurred. Progesterone (50 mg) was injected on the Case Report
360
Toni et al.
day of oocyte retrieval, and 30 mg was given daily from the next day for 13 days. Nine days after transfer, the patient complained of lower abdominal distension, and ovarian syndrome (OHSS) was hyperstimulation revealed by ultrasound. Twelve days after transfer, serum /3-HCG was detected by immunoassay (Stratus, Baxter enzyme Healthcare Co.) and pregnancy was diagnosed. At 5 weeks gestation, ultrasound examination showed that there was one gestational sac (GS) in the uterine cavity and that the bilateral ovaries were enlarged as a result of OHSS; the right ovary was 111 mm, and the left one was 136 mm in the greatest dimenstion. At 6 weeks gestation, fetal heart movement (FHM) was seen and the size of the ovaries had not changed. The patient presented at 9 weeks gestation, complaining of slight brown discharge. A pelvic examination showed that the cervix was closed and there was slight bleeding. Ultrasound showed one GS in the uterine cavity with a crown-rump length (CRL) of 32 mm, and another GS with a fetal echo was newly discovered in the right adnexal region, and the diagnosis of combined intrauterine and ectopic pregnancy was made. The ectopic GS was 32 mm in diameter and the fetus in it had a CRL of 18 mm and FHM. The patient was immediately admitted to the hospital. Because it was close to the fundus uteri, a tubal interstitial pregnancy was considered, and we thought it would be difficult to remove the interstitial portion without damaging the normally implanting fetus. Operative maneuvers were discussed, and after 2 days, pre-operative ultrasound examination showed that the FHM of the ectopic pregnancy was gone and that the ectopic pregnancy was not interstitial because the GS was in a cul de sac (Fig. 1). It was expected that the GS of the ectopic pregnancy would not be enlarged and that rupture of the GS would not occur because the fetus was dead. Therefore, surgery was deferred and the patient was carefully observed in the hospital. Int J Gynecol Obstet 33
Fig. 1. Transabdominal ultrasound shows two gestational sacs; one in the uterine cavity (GSl), the other in a cul de sac (GS2).
Follow-up with ultrasound showed that there was no growth of the GS of the ectopic pregnancy and that there might be organization of the GS because of thickening of the wall and increase in internal echo density. At 12 weeks gestation, the biparietal diameter of the fetus in the uterine cavity was 25 mm, compatible with the gestational age. Since the GS of the ectopic pregnancy tended to be small, with a diameter of 29 x 26 mm, it was considered that there was little risk of rupture of the ectopic pregnancy, and the patient was discharged from the hospital. The remaining antenatal course was uneventful, and the GS of the ectopic pregnancy was never found by ultrasound after 16 weeks gestation because of the enlarged uterus. At 37 weeks gestation a healthy female infant was delivered normally. The next day, a small laparotomy was achieved. A thumb-head sized swollen lesion was found in the right tube, and a right salpingectomy was performed. Histological investigation of this lesion found the presence of bones and striated muscles with degeneration in a hematoma close to the tubal epithelium, and these tissues were thought to be those of the fetus of the ectopic pregnancy (Figs. 2,3). The distance between the hematoma and the serous membrane was below 1 mm.
Combinedpregnancy after IVF-ET
Fig. 2. A bone and striated muscles in the right oviduct (H & E, x 40).
Discussion A combined intrauterine and extrauterine pregnancy had been thought to be very rare, occurring in only one in 30,000 pregnancies [3]. But recent literature indicates that this condition is more common than originally thought. This increase in combined intrauterine and extrauterine pregnancy is due to the rising frequency of ectopic pregnancy and the use of ovulation inducing agents [7].
Fig. 3. The distance of the old hematoma of the ectopic pregnancy (arrows) and the serous membrane was below 1 mm (H &E, x40).
361
A combined pregnancy is constituted of an ectopic pregnancy and multiple gestation, and IVF-ET is a risk factor of both of them. The incidence of ectopic pregnancy is 1.6-4.6% after IVF-ET, which is higher than that in natural reproduction (0.4- 1070) [2]. There are some theoretic factors that may predispose to ectopic pregnancy following ET. These include uterine cramping, traumatic ET with uterine bleeding [12] and a large amount of transfer medium [15], all of which may result in retrograde delivery of the embryos to the fallopian tube. Other factors are exposure to diethylstilbesterol (DES) which widens the interstitial and isthmic portions of the oviducts [9], and damaged tubes which do not have the ability to expel trapped embryos into the uterus [5]. In this patient, the volume of transfer medium was only 15 ~1, but insertion of the ET catheter was so difficult that sounding of the cervix was needed. The patient did not have cramping but there was slight uterine bleeding at the time of transfer, and she had damaged tubes; those may predispose to a tubal pregnancy. Multiple embryo replacement has been shown to increase the incidence of pregnancy after IVF-ET, but this also causes IVF-ET to be a risk of multiple pregnancy [8,15]. The patient received a four embryo transfer, and, unfortunately, twin gestation occurred, one in the uterine cavity and the other in the right fallopian tube. There are seven case reports on combined intrauterine and ectopic pregnancy after IVFET and one after GIFT (Table I) [1,4,6,1013,161. Two of the patients had a T-shaped uterus due to DES yexposure, and four had damaged tubes, which may be risk factors as previously stated. All of them received multiple embryo or oocyte transfer resulting in multiple implantation. In this patient, though intrauterine GS was detected at 5 weeks gestation, the tubal GS was never discovered before 9 weeks gestation. The reason for the delayed diagnosis was OHSS, which made it difficult to observe the details in the adnexal regions, and the Case Report
[ 131
“The intratuerine
Tani et al.
Spandoni
Dicker et al. [4] Clamberdella et al. [6]
(-1
GIFT
4 3 oocytes
Long term infertility
fetus survived
after surgery,
Tubal damage
but was revealed
to be with trisomy
21 by amniocentesis.
(-1
4
(+)
(+) Slight bleeding
None
(+l
2 15pI
(+]
30 PI
4
T-shaped uterus (DES-exposure) Tubal damage
Tubal damage
(+l
g ~1
6
Tubal damage
Porter et al. [lo] Synder et al. [ll]
70 cl1
6
(+l
(+]
30 ill
None
5
Intraperitoneal bleeding
50 pl
Complications in ET
pregnancies.
5
and extrauterine
T-shaped uterus (DES-exposure) Pelvic inflammatory disease Endometriosis
Sondheimer et al. (121 Yovitch et al. [16] Bearman et al. [l]
NO.
intrauterine Volume of transfer medium
Indication for IVF-ET
Authors
of combined
of embryos
Review of case reports
Table I.
None
Performed
Performed
Performed
at 19 Normal labor at 37 weeks gestation Normal albor at 37 weeks gestation
Therapeutic abortion weeks gestation’
Ongoing
Normal labor at 37 weeks gestation Ongoing
Performed Performed
Normal labor at 40 weeks gestation
Premature labor at 33 weeks gestation, twins Ongoing
Prognosis
Performed
Performed
Performed
Emergency surgery
Combinedpregnancy
intrauterine GS made us not consider the possibility of a combined pregnancy. Furthermore, all of reported cases except one had symptoms or signs of intra-abdominal bleeding or shock, whereas this patient fortunately had none of them (Table I). Because IVF-ET is a risk factor of not only ectopic pregnancy but also combined pregnancy; the possibility of combined intrauterine and tubal pregnancy in pregnant patients following IVF-ET must always be considered. The patient was managed without surgery after the diagnosis and was carefully observed for 3 weeks in the hospital. Because tubal rupture of the ectopic pregnancy is a life-threatening event, the intrauterine fetuses of all reported cases have survived after surgery, and the distance between the hematoma and the serous membrane of the removed oviduct in this patient was below 1 mm, it is emphasized that surgery must be performed as soon as combined pregnancy is diagnosed.
6
7
8
9
10
11
12
13 14
References 15 Bearman DM, Vieta PA, Snipes RD, Gobien RP, Garcia JE, Rosenwaks Z: Heterotopic pregnancy after in vitro fertilization and embryo transfer. Fertil Steril 45: 719, 1986. Cohen J: Pregnancy, abortion and birth after in vitro fertilization. In: In Vitro Fertilization, p. 135. IRS Press, Washington, DC, 1986. DeVoe RW, Pratt JH: Simultaneous intrauterine and extrauterine pregnancy. Am J Obstet Gynecol 56: 1119, 1948. Dicker D, Goldman G, Feldberg D, Ashkenazi J, Goldman JA: Heterotopic pregnancy after IVF-ET: report of a case and a review of the literature. Hum Reprod 4: 335, 1989. Dor J, Rudak R, Mashiach S, Goldman B, Nebel L: Unilateral tubal twin pregnancy following in vitro fertilization and embryo transfer. Fertil Steril42: 297, 1984.
16
after IVF-ET
363
Gamberdella FR, Marrs RP: Heterotopic pregnancy associated with assisted reproductive technology. Am J Obstet GynecolZ60: 1520, 1989. Hann LE, Bachman DM, McArdle CR: Coexistent intrauterine and ectopic pregnancy: a reevaluation. Radiology 152: 151, 1984. Kerin JFP, Quinn PC, Kirby C, Seamark RF, Warnes GM, Jeffrey R, Matthews CD, Cox LW: Incidence of multiple pregnancy after in-vitro fertilization and embryo transfer. Lancet ii: 537, 1983. Muasher SJ, Garcia JE, Jone HW Jr: Experience with diethylstilbesterol-exposed infertile women in a program of in vitro fertilization, Fertil Steril42: 20, 1984. Porter R, Smith B, Ahuja K, Tucker M, Craft I: Combined twin ectopic pregnancy and intrauterine gestation following in-vitro fertilization. J In Vitro Fertil Embryo Transfer 3; 330,1986. Synder T, delCastillo J, Graff J, Hoxsey R, Hefti M: Heterotopic pregnancy after in vitro fertilization and ovulatory drugs. Emergency Med 17: 846,1988. Sondheimer SJ, Turek RW, Blasco L, Strauss J III, Arger P, Mennuti M: Simultaneous ectopic pregnancy with intrauterine twin gestations after in vitro fertilization and embryo transfer. Fertil Steri143: 313, 1985. Spadoni LR: Discussion. Am J Obstet Gynecol160: 1522, 1989. Steptoe PC, Edwards RG: Reimplantation of a human embryo with subsequent tubal pregnancy. Lancet i: 880, 1976. Webster J: Embryo replacement. In: In vitro Fertilization, p. 127. IRS Press, Washington, DC, 1986. Yovitch JL, McColm SC, Turner SR, Matson PL: Heterotopic pregnancy from in-vitro fertilization. J In Vitro Fertil Embryo Transfer 2: 146, 1985.
Address for reprints. H. Tani Department of Obstetrics and Gynecology Niigata University School of Medicine 1 Asohimschi Dori Niigrta, Japan
Case Report
359
Combined intrauterine and tubal fertilization and embryo transfer H. Tani, K. Oda, K. Schichiri,
0. Arakawa
pregnancy
after in vitro
and Y. Sato
Department of Obstetrics and Gynecology, Niigata University, School of Medicine, I Asahimachi Dori, Niigata (Japan) (Received July 14th. 1989) (Revised and accepted September 21st, 1989)
Abstract
A case of combined intrauterine and tubal pregnancy after in vitro fertilization and embryo transfer is reported. As soon as the diagnosis was made at 9 weeks gestation, the fetal heart movement of the tubal pregnancy disappeared, and the patient was managed without surgery throughout the pregnancy course. After an infant was delivered, a right salpingectomy was performed and the diagnosis was histologically confirmed. Risk factors and treatments of combined pregnancy are discussed. Keywords: Combined (heterotopic) nancy; IVF-ET; Ectopic pregnancy.
preg-
Introduction
The techniques of in vitro fertilization and embryo transfer (IVF-ET) have been widely used as a treatment for infertility. However, some abnormal results have been reported; for example, ectopic pregnancy and multiple gestation. The first pregnancy after IVF-ET was a tubal pregnancy [14]. Since then, some reports have drawn attention to this possibility [2]. Combined intrauterine and tubal pregnancy, one of the rare conditions of ectopic 0020-7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
pregnancy, occurs in approximately one in 30,000 pregnancies [3]. We describe a case of a combined intrauterine and tubal pregnancy after IVF-ET and review some reported cases. Case report
The patient was a 25year-old woman with primary sterility. Bilateral tubal occlusion was suspected by hysterosalpingography. Laparoscopic examination revealed normal patency of the bilateral oviduct, but bilateral severe perifimbrial adhesions were found. The patient underwent laparoscopic fimbriolysis at the same time. Pregnancy failed to occur after 12 months observation and IVFET was considered. Ovarian hyperstimulation was achieved with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG). On day 13, eight oocytes were collected transvaginally by ultrasound, and were incubated and inseminated. Eighteen hours after sperm addition, normal fertilization of four oocytes was confirmed. Forty-eight hours after oocyte retrieval, four embroys were transferred in 15 ~1 of medium into the uterine cavity. At this time, the sounding of the cervix was needed because it was difficult to insert the ET catheter, and slight bleeding occurred. Progesterone (50 mg) was injected on the Case Report
360
Toni et al.
day of oocyte retrieval, and 30 mg was given daily from the next day for 13 days. Nine days after transfer, the patient complained of lower abdominal distension, and ovarian syndrome (OHSS) was hyperstimulation revealed by ultrasound. Twelve days after transfer, serum /3-HCG was detected by immunoassay (Stratus, Baxter enzyme Healthcare Co.) and pregnancy was diagnosed. At 5 weeks gestation, ultrasound examination showed that there was one gestational sac (GS) in the uterine cavity and that the bilateral ovaries were enlarged as a result of OHSS; the right ovary was 111 mm, and the left one was 136 mm in the greatest dimenstion. At 6 weeks gestation, fetal heart movement (FHM) was seen and the size of the ovaries had not changed. The patient presented at 9 weeks gestation, complaining of slight brown discharge. A pelvic examination showed that the cervix was closed and there was slight bleeding. Ultrasound showed one GS in the uterine cavity with a crown-rump length (CRL) of 32 mm, and another GS with a fetal echo was newly discovered in the right adnexal region, and the diagnosis of combined intrauterine and ectopic pregnancy was made. The ectopic GS was 32 mm in diameter and the fetus in it had a CRL of 18 mm and FHM. The patient was immediately admitted to the hospital. Because it was close to the fundus uteri, a tubal interstitial pregnancy was considered, and we thought it would be difficult to remove the interstitial portion without damaging the normally implanting fetus. Operative maneuvers were discussed, and after 2 days, pre-operative ultrasound examination showed that the FHM of the ectopic pregnancy was gone and that the ectopic pregnancy was not interstitial because the GS was in a cul de sac (Fig. 1). It was expected that the GS of the ectopic pregnancy would not be enlarged and that rupture of the GS would not occur because the fetus was dead. Therefore, surgery was deferred and the patient was carefully observed in the hospital. Int J Gynecol Obstet 33
Fig. 1. Transabdominal ultrasound shows two gestational sacs; one in the uterine cavity (GSl), the other in a cul de sac (GS2).
Follow-up with ultrasound showed that there was no growth of the GS of the ectopic pregnancy and that there might be organization of the GS because of thickening of the wall and increase in internal echo density. At 12 weeks gestation, the biparietal diameter of the fetus in the uterine cavity was 25 mm, compatible with the gestational age. Since the GS of the ectopic pregnancy tended to be small, with a diameter of 29 x 26 mm, it was considered that there was little risk of rupture of the ectopic pregnancy, and the patient was discharged from the hospital. The remaining antenatal course was uneventful, and the GS of the ectopic pregnancy was never found by ultrasound after 16 weeks gestation because of the enlarged uterus. At 37 weeks gestation a healthy female infant was delivered normally. The next day, a small laparotomy was achieved. A thumb-head sized swollen lesion was found in the right tube, and a right salpingectomy was performed. Histological investigation of this lesion found the presence of bones and striated muscles with degeneration in a hematoma close to the tubal epithelium, and these tissues were thought to be those of the fetus of the ectopic pregnancy (Figs. 2,3). The distance between the hematoma and the serous membrane was below 1 mm.
Combinedpregnancy after IVF-ET
Fig. 2. A bone and striated muscles in the right oviduct (H & E, x 40).
Discussion A combined intrauterine and extrauterine pregnancy had been thought to be very rare, occurring in only one in 30,000 pregnancies [3]. But recent literature indicates that this condition is more common than originally thought. This increase in combined intrauterine and extrauterine pregnancy is due to the rising frequency of ectopic pregnancy and the use of ovulation inducing agents [7].
Fig. 3. The distance of the old hematoma of the ectopic pregnancy (arrows) and the serous membrane was below 1 mm (H &E, x40).
361
A combined pregnancy is constituted of an ectopic pregnancy and multiple gestation, and IVF-ET is a risk factor of both of them. The incidence of ectopic pregnancy is 1.6-4.6% after IVF-ET, which is higher than that in natural reproduction (0.4- 1070) [2]. There are some theoretic factors that may predispose to ectopic pregnancy following ET. These include uterine cramping, traumatic ET with uterine bleeding [12] and a large amount of transfer medium [15], all of which may result in retrograde delivery of the embryos to the fallopian tube. Other factors are exposure to diethylstilbesterol (DES) which widens the interstitial and isthmic portions of the oviducts [9], and damaged tubes which do not have the ability to expel trapped embryos into the uterus [5]. In this patient, the volume of transfer medium was only 15 ~1, but insertion of the ET catheter was so difficult that sounding of the cervix was needed. The patient did not have cramping but there was slight uterine bleeding at the time of transfer, and she had damaged tubes; those may predispose to a tubal pregnancy. Multiple embryo replacement has been shown to increase the incidence of pregnancy after IVF-ET, but this also causes IVF-ET to be a risk of multiple pregnancy [8,15]. The patient received a four embryo transfer, and, unfortunately, twin gestation occurred, one in the uterine cavity and the other in the right fallopian tube. There are seven case reports on combined intrauterine and ectopic pregnancy after IVFET and one after GIFT (Table I) [1,4,6,1013,161. Two of the patients had a T-shaped uterus due to DES yexposure, and four had damaged tubes, which may be risk factors as previously stated. All of them received multiple embryo or oocyte transfer resulting in multiple implantation. In this patient, though intrauterine GS was detected at 5 weeks gestation, the tubal GS was never discovered before 9 weeks gestation. The reason for the delayed diagnosis was OHSS, which made it difficult to observe the details in the adnexal regions, and the Case Report
[ 131
“The intratuerine
Tani et al.
Spandoni
Dicker et al. [4] Clamberdella et al. [6]
(-1
GIFT
4 3 oocytes
Long term infertility
fetus survived
after surgery,
Tubal damage
but was revealed
to be with trisomy
21 by amniocentesis.
(-1
4
(+)
(+) Slight bleeding
None
(+l
2 15pI
(+]
30 PI
4
T-shaped uterus (DES-exposure) Tubal damage
Tubal damage
(+l
g ~1
6
Tubal damage
Porter et al. [lo] Synder et al. [ll]
70 cl1
6
(+l
(+]
30 ill
None
5
Intraperitoneal bleeding
50 pl
Complications in ET
pregnancies.
5
and extrauterine
T-shaped uterus (DES-exposure) Pelvic inflammatory disease Endometriosis
Sondheimer et al. (121 Yovitch et al. [16] Bearman et al. [l]
NO.
intrauterine Volume of transfer medium
Indication for IVF-ET
Authors
of combined
of embryos
Review of case reports
Table I.
None
Performed
Performed
Performed
at 19 Normal labor at 37 weeks gestation Normal albor at 37 weeks gestation
Therapeutic abortion weeks gestation’
Ongoing
Normal labor at 37 weeks gestation Ongoing
Performed Performed
Normal labor at 40 weeks gestation
Premature labor at 33 weeks gestation, twins Ongoing
Prognosis
Performed
Performed
Performed
Emergency surgery
Combinedpregnancy
intrauterine GS made us not consider the possibility of a combined pregnancy. Furthermore, all of reported cases except one had symptoms or signs of intra-abdominal bleeding or shock, whereas this patient fortunately had none of them (Table I). Because IVF-ET is a risk factor of not only ectopic pregnancy but also combined pregnancy; the possibility of combined intrauterine and tubal pregnancy in pregnant patients following IVF-ET must always be considered. The patient was managed without surgery after the diagnosis and was carefully observed for 3 weeks in the hospital. Because tubal rupture of the ectopic pregnancy is a life-threatening event, the intrauterine fetuses of all reported cases have survived after surgery, and the distance between the hematoma and the serous membrane of the removed oviduct in this patient was below 1 mm, it is emphasized that surgery must be performed as soon as combined pregnancy is diagnosed.
6
7
8
9
10
11
12
13 14
References 15 Bearman DM, Vieta PA, Snipes RD, Gobien RP, Garcia JE, Rosenwaks Z: Heterotopic pregnancy after in vitro fertilization and embryo transfer. Fertil Steril 45: 719, 1986. Cohen J: Pregnancy, abortion and birth after in vitro fertilization. In: In Vitro Fertilization, p. 135. IRS Press, Washington, DC, 1986. DeVoe RW, Pratt JH: Simultaneous intrauterine and extrauterine pregnancy. Am J Obstet Gynecol 56: 1119, 1948. Dicker D, Goldman G, Feldberg D, Ashkenazi J, Goldman JA: Heterotopic pregnancy after IVF-ET: report of a case and a review of the literature. Hum Reprod 4: 335, 1989. Dor J, Rudak R, Mashiach S, Goldman B, Nebel L: Unilateral tubal twin pregnancy following in vitro fertilization and embryo transfer. Fertil Steril42: 297, 1984.
16
after IVF-ET
363
Gamberdella FR, Marrs RP: Heterotopic pregnancy associated with assisted reproductive technology. Am J Obstet GynecolZ60: 1520, 1989. Hann LE, Bachman DM, McArdle CR: Coexistent intrauterine and ectopic pregnancy: a reevaluation. Radiology 152: 151, 1984. Kerin JFP, Quinn PC, Kirby C, Seamark RF, Warnes GM, Jeffrey R, Matthews CD, Cox LW: Incidence of multiple pregnancy after in-vitro fertilization and embryo transfer. Lancet ii: 537, 1983. Muasher SJ, Garcia JE, Jone HW Jr: Experience with diethylstilbesterol-exposed infertile women in a program of in vitro fertilization, Fertil Steril42: 20, 1984. Porter R, Smith B, Ahuja K, Tucker M, Craft I: Combined twin ectopic pregnancy and intrauterine gestation following in-vitro fertilization. J In Vitro Fertil Embryo Transfer 3; 330,1986. Synder T, delCastillo J, Graff J, Hoxsey R, Hefti M: Heterotopic pregnancy after in vitro fertilization and ovulatory drugs. Emergency Med 17: 846,1988. Sondheimer SJ, Turek RW, Blasco L, Strauss J III, Arger P, Mennuti M: Simultaneous ectopic pregnancy with intrauterine twin gestations after in vitro fertilization and embryo transfer. Fertil Steri143: 313, 1985. Spadoni LR: Discussion. Am J Obstet Gynecol160: 1522, 1989. Steptoe PC, Edwards RG: Reimplantation of a human embryo with subsequent tubal pregnancy. Lancet i: 880, 1976. Webster J: Embryo replacement. In: In vitro Fertilization, p. 127. IRS Press, Washington, DC, 1986. Yovitch JL, McColm SC, Turner SR, Matson PL: Heterotopic pregnancy from in-vitro fertilization. J In Vitro Fertil Embryo Transfer 2: 146, 1985.
Address for reprints. H. Tani Department of Obstetrics and Gynecology Niigata University School of Medicine 1 Asohimschi Dori Niigrta, Japan
Case Report