Heterotopic pregnancy

K. Birundha

Department of Obstetrics and Gynecology, Kauvery Hospital, Hosur, India


Heterotopic pregnancy (HP) incidence is increasing recently due to advanced artificial reproductive techniques. Incidence is 1 in 30000 in natural conception cycles. It is as high as 1in 100 to 1in 500 in Assisted Reproductive Technology (ART) pregnancies (1a). Heterotopic triplet pregnancy is rare but potentially life-threatening condition in which simultaneous gestation occurs in two or more implantation sites. Here we report a case of triplet heterotopic pregnancy resulting from ovulation induction and timed intercourse cycle. It was an intrauterine Dichorionic Diamniotic (DCDA) twin with a right single tubal ectopic pregnancy.

Case Presentation

A 25- years-old female presented to OPD four years ago for infertility treatment.

She was known to have Polycystic Ovary Syndrome (PCOD) and first-degree consanguineous marriage. She was managed with Myoinnositol and Metformin. Previous infertility treatment included failed intrauterine insemination (IUI)-three years ago. She had diagnostic laparoscopy and ovarian drilling in the past.

On her first visit, she had basic infertility investigations of USG abdomen and Hormone profile. USG abdomen showed both ovaries to be mildly enlarged in size and also multiple peripherally arranged follicles suggestive of bilateral polycystic ovaries. Thyroid Function Tests (TFT) and prolactin were normal.

She conceived with infertility treatment in the first cycle. Nuchal Translucency (NT) scan showed lethal skeletal dysplasia at 14 weeks and termination of pregnancy was done.

She came back for infertility treatment again in a year. She conceived again with ovulation induction (Clomiphene citrate and Gonadotrophins) and timed intercourse in the second cycle. She was started with Progestogen and Human Chorionic Gonadotrophin (HCG) injection to support the pregnancy. Plan was for a scan after two weeks.

But she presented at 6 weeks of gestation with acute lower abdominal pain.

Initial Trans-vaginal Ultrasound scan showed twin intrauterine pregnancy of 6 to 7 weeks with mild subchorionic bleed. Conservative treatment for pain was given. As the pain didn’t settle, an abdomen and pelvic scan were done to rule out any other causes for acute abdominal pain. It revealed a live twin intrauterine pregnancy of 6 to 7 weeks gestation with a complex mass of size 4.5 x 2.2 cm, with the central sac, in the right adnexa. No other abnormality was noted.

It was suspicious of heterotopic right tubal pregnancy. She was advised MRI pelvis for further evaluation which indicated diamniotic dichorionic twin live intrauterine pregnancy with complex right adnexal mass lesion, associated with mild haemo-peritoneum, suggestive of ruptured right tubal ectopic pregnancy.

The patient was counselled for emergency laparoscopic right salpingectomy without compromising the intrauterine pregnancy. Consent was taken after explaining the risk of miscarriage, and anesthetic risk to the fetus. Intraoperatively, she was noted to have ruptured right tubal ectopic with mild haemoperitoneum. The right ovary and left tube and ovary were normal.

She continued her pregnancy with close monitoring. NT scan done at a fetal medicine scan center showed a DCDA twin with fetus A of normal NT and fetus B showed anhydramnios. Structural evaluation could not be completed due to anhydramnios. Counseling was given regarding the prognosis with the anhydramniotic twin. Anhydramnios was managed conservatively. Followup scan after 10 days showed the same findings. Repeat scan at 19-20 weeks showed fetus A with normal liquor and no gross anomalies. Fetus B (previous anhydraminiotic twin) showed adequate liquor with bilateral talipes foot and the rest of the structures were normal.

Followup scan at 23 weeks: Fetus A with no major anomalies, normal liquor. Fetus B is of normal liquor and no major anomalies except bilateral talipes foot.

At 25 weeks she came with h/o leaking PV. USG scan showed normal liquor and clinically no PV leak was noted. Admitted and managed conservatively with monitoring for signs of infection/sepsis. Betnesol, two doses, was given for fetal lung maturity.

She was discharged after five days and reviewed every week at OPD. Re-admitted at 28 weeks with abdominal tightening and PV leak. Clinically PV leak was confirmed with no cervical dilatation. USG showed fetus A with normal liquor and fetus B with reduced liquor and normal doppler in both twins. She has explained the risk of pre-term labor, prematurity, sepsis, fetal respiratory distress, IUD, need for long-term NICU care.

She was shifted to a higher centre with a NICU facility for further management where she underwent emergency LSCS and delivered both fetuses. Fetus A(female) was alive and healthy and Fetus B (male fetus with bilateral talipes) didn’t survive after 24 h of birth.

Heterotopic-pregnancy-1Fig. 1. Scan showing Intrauterine Twin gestational sac.

Heterotopic-pregnancy-2Fig. 2. Scan showing adnexal mass.

Heterotopic-pregnancy-3Fig. 3. Anomaly scan with abdomen view of twins.

Heterotopic-pregnancy-4Fig. 4. Anomaly scan with brain view of Twins.


Heterotopic pregnancy can give a variable clinical presentation including unilateral or bilateral tubal, cervical, abdominal, and ovarian pregnancies. Risk factors for triplet heterotopic pregnancy are similar to any heterotopic pregnancy. They are pelvic inflammatory disease, tubal surgery, endometriosis, previous ectopic pregnancy, failed intrauterine contraceptive device, tubal sterilization, cigarette smoking, IVF, Gamete intrafallopian transfer (GIFT), and ovulation induction. Diagnosis is difficult because of the asymptomatic nature of the condition. Around 50% of heterotopic pregnancies are asymptomatic [5]. Most of them (78.5%) are diagnosed after the rupture of the tube, with acute abdomen symptoms [6]. The major symptoms are abdominal pain – 83%, acute abdomen symptoms, and shock – 13%, and vaginal bleeding – 50% of cases [2]. The implantation of an embryo in the wall of the fallopian tube bears a high risk of rupture because the rich local vascularization and trophoblast invasion may cause tubal rupture even if there is no fetal cardiac activity.

The most frequent location of extrauterine pregnancy coexisting with intrauterine pregnancy is oviducts (93.9%); more rarely the pregnancy is located in the ovary (6%) [1]. Only in 57% of cases reported in the literature the diagnosis of heterotopic triplets was preoperatively made [6]. Unless enlarged, the ectopic gestational sac can easily be missed on an ultrasound scan, and the intermittent unilateral pain can be attributed to a hemorrhagic corpus luteum or ovarian hyperstimulation.

It is proved that in patients treated because of infertility and who underwent in vitro fertilization the risk of heterotopic pregnancy increases 400-fold in comparison to natural conception. It is also thought that the incidence of this pathology after the use of ART oscillates from 0.75 to 1.3% [3]. The reasons are preexisting tubal disease, the number of embryo transfers, and techniques for embryo transfer. In cases of heterotopic pregnancy following IVF the diagnosis can be exceptionally difficult. The beta-human chorionic gonadotropin (β-hCG) may continue to rise normally. It is reported that approximately 70% of heterotopic pregnancies are diagnosed between 5 and 8 weeks of gestation, 20% are diagnosed between 9 and 10 weeks, and the remaining 10% are diagnosed after 11 weeks [2,4].

Finally, the diagnosis should not be missed when a woman with a known intrauterine pregnancy presents with abdominal pain due to peritoneal irritation, hemoperitoneum, and hypovolemic shock. The purpose of the treatment is to interrupt the development of the ectopic pregnancy and preserve the intrauterine pregnancy.

The therapeutic options vary. Most cases of HP with tubal pregnancy have been treated surgically. The most frequently described treatment is surgical, by removal of the uterine tube(salpingectomy) by laparotomy or laparoscopy. Traditionally, laparoscopic treatment has been used to treat unruptured ectopic pregnancies at a small gestational age, while laparotomy has been used for ruptured ectopic [6,2]. Although the long-term effects of laparoscopic surgery during pregnancy on the fetus have not been well studied [6,7], laparoscopy has been increasingly used in surgical procedures in pregnant women and according to the literature no increase in adverse outcomes has been reported [6,8]. Conservative treatment by locally injecting potassium chloride or hyperosmolar glucose is an option in cases of cervical heterotopic pregnancy [4]. The use of methotrexate has detrimental effects on the ongoing intrauterine pregnancy and so it is not an alternative [4,6]. A review of the literature by Goldstein et al. revealed that 55% of tubal heterotopic pregnancies treated by potassium chloride injection required subsequent salpingectomy which disputes the suitability of the method [9].

During the surgery, the uterus should be minimally manipulated to prevent uterine contractions during or after the operation. Nevertheless, special attention should be paid to prevent the disruption of the ovarian blood supply, particularly in the ovary bearing the corpus luteum. In case of disturbance of the corpus luteum up to 12 weeks of gestation, progesterone support is indicated [6]. In our case, we proceeded immediately to laparoscopic right Salpingectomy under spinal anesthesia after the diagnosis was established.

It is estimated that intrauterine pregnancy continued normally after the removal of extrauterine pregnancy in 65-92% of cases [1,2]. Reece et al [1] submitted an analysis of 37 patients with diagnosed heterotopic pregnancy after surgical treatment of extrauterine pregnancy – 75.6% gave birth around their expected delivery date, 16.2% prematurely and 3% of pregnancies ended with a miscarriage. In our case, the course of the intrauterine twin pregnancy was normal till 28 weeks of gestation and the patient had a pre-term rupture of membranes, was delivered by LSCS, fetus A survived and fetus B didn’t survive.


In conclusion, it is important to understand the need for systematic assessment of the uterus and adnexa during the first ultrasound scan of the pregnancy performed at 7-8 weeks of gestation, even if an intrauterine gestational sac is already confirmed and even if there is no apparent risk factor. It is a fact that the diagnosis of Heterotopic pregnancy tends to be overlooked after confirming the intrauterine pregnancy. High Index of suspicion is needed when the patient has undergone IVF or if tubal pathology is suspected. When a diagnosis is established on time and treated, the rate of pregnancies that reach term after treatment is significant. Heterotopic pregnancy in ART-assisted pregnancies can be avoided by limiting the number of embryos transferred and embryo transfer techniques as per guidelines established by international committees for assisted reproductive technology.


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Dr. K. Birundha

Consultant Obstetrician & Gynaecologist Specialist in Infertility