Journal of Obstetrics and Gynaecology, 2014; Early Online: 1–2 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online
CASE REPORT
Early diagnosis of heterotopic triplet pregnancy with an intrauterine and bilateral tubal pregnancy after IVF: A case report
J Obstet Gynaecol Downloaded from informahealthcare.com by UMEA University Library on 04/02/15 For personal use only.
D. I. P. Buca, D. Murgano, G. Impicciatore, A. P. Castigliego, C. Iannantuono, M. Leombroni, E. Falò & M. Liberati Obstetrics and Gynecology Unit, “SS.Annunziata” Hospital Chieti, Chieti, Italy and “G. d’Annunzio” University Chieti-Pescara, Chieti, Italy DOI: 10.3109/01443615.2014.993940 Correspondence: Buca Danilo Italo Pio, Obstetrics and Gynecology Unit, G. d’Annunzio University Chieti-Pescara, Via dei Vestini, 5 66100 Chieti, Italy. Tel: 0871/358247. E-mail: [email protected]
Introduction Heterotopic pregnancy (HP) is a rare condition defined as the simultaneous presence of intrauterine pregnancy (IUP) and ectopic pregnancy (EP). It occurs in around 1/30000 of spontaneous pregnancies (Sun et al. 2012). Recently, HP has increased due to several factors: tubal damage induced by pelvic inflammatory disease (PID), previous tubal surgeries, ovarian stimulation and transfer of many embryos using assisted reproductive techniques (ART) (Felekis et al. 2014). It has increased up to 1% using ART (Chin et al. 2004; Li et al. 2013). The early diagnosis of HP is often difficult to detect because 50% of these pregnancies are asymptomatic (Sun et al. 2012). In this article, we describe a rare case of heterotopic triplet pregnancy with bilateral tubal and IUP diagnosed by trans-vaginal ultrasound (TVU) after intracytoplasmic sperm injection and embryo transfer (ICSI-ET). The objective of this article is to underline the need for an increased clinical awareness of this condition during the first-trimester TVU, even in the presence of an intrauterine gestational sac and when predisposing factors are known particularly with regard to in-vitro fertilisation (IVF).
Case report A 37-year-old Caucasian woman who had a 5-year history of idiopathic infertility underwent ICSI-ET in December 2012. In effect, at the time of treatment, three grade-A embryos were transferred 72 hours after oocytes injection (JOINT SOGC-CFAS 2008). There was no history of PID or tubal surgery and tubal patency was revealed on hysterosalpingography. Two weeks following ICSI-ET, the betahuman chorionic gonadotrophin (hCG) value was 125mIU/ml; it increased to 494mUI/ml on day 16 and to 1916mUI/ml on day 21. In this period the first TVU was performed. This examination revealed an intrauterine gestational sac and suspicious images in the fallopian tubes, in particular, on the right adnexal side, TVU revealed a round anechoic lesion with an inside yolk sac, indicative of a right tubal pregnancy. In the left adnexal area, medial to the ovary, TVU displayed a hypoechoic lesion that could be referred to as a haematocele due to a left tubal pregnancy. The endometrium appeared decidualised, and a rounded anechoic lesion was found inside the uterine cavity; this image could be referred to as a gestational sac. In the pouch of Douglas there was a fine corpuscular free fluid (Figure 1). On admission, the patient had no vaginal bleeding and no abdominal pain. We decided to perform a laparoscopic procedure and as expected, during surgery both tubal pregnancies were confirmed. Then a bilateral salpingectomy was performed. A histopathological examination confirmed the presence of
trophoblastic tissue in both the fallopian tubes. In the post-operative period, vaginal bleeding was reported and TVU revealed the spontaneous abortion of IUP. Thirty days following surgery the beta-hCG dosage was negative.
Discussion The simultaneous presence of a bilateral tubal and IUP is a rare condition and early diagnosis remains a challenge. The most important aid in the diagnosis of HP is the utilisation of high-resolution TVU. Detection of TVU is often difficult because HP maybe obscured by the presence of IUP. False negative results have been associated with markedly enlarged ovaries after ovulation induction that could mask an ectopic pregnancy (Pan et al. 2002). According to Tal et al. (1996) and Barrenetxea et al. (2007), a preoperative diagnosis is possible in a limited number of cases (41.07% and 26.25%, respectively). In contrast, Li et al. evaluating a cohort of 16483 pregnancies conceived by IVF detected 122 HPs using TVU. In particular, 72.0% of HPs were diagnosed between 5 and 6 weeks, 15.9% between 7 and 8 weeks and only 4.5% after 9 weeks (Li et al. 2013). The majority of authors recommend performing TVU at 4–6 weeks following embryo transfer (corresponding to 6–8 weeks’ gestation) (Guirgis and Craft 1991; Sentilhes et al. 2009). The present report demonstrates that an early diagnosis of simultaneous bilateral tubal pregnancy is possible using a high-resolution TVU performed on day 21 following ET (corresponding to 5 weeks’ gestation), even if an intrauterine gestational sac is already confirmed and there is no apparent risk factor. Moreover, this case suggests that adnexal sites should be assessed carefully in IVF-treated patients also in the presence of an intrauterine pregnancy. The aim of a correct early diagnosis is to evaluate the correct management of HP. The main objective is to preserve the IUP and to stop or remove the ectopic ones. The management of HP remains controversial. Surgical removal of HP offers an advantage as opposed to medical treatment (local or systemic methotrexate) or expectant management. Expectant management is possible only in selected patients with unruptured gestation and a downward trend of betahCG. Obviously, systemic methotrexate therapy is not warranted in HP because of the presence of IUP. In our particular case, because of the suspicion of a bilateral tubal pregnancy, we decided to carry out radical surgical treatment in agreement with the patient. This choice was made to reduce the risk of tubal rupture (uptrend of beta-hCG) and the resulting haemoperitoneum with hypovolemic shock. The decision to perform surgery during pregnancy must always take into consideration the potential foetal risks without compromising the safety of the mother. To preserve the IUP pregnancy, during surgery the anaesthetist prevented episodes of hypoxia and hypovolemia by monitoring the mother’s blood pressure and end-tidal CO2. In fact, during laparoscopic surgeries there are potential risks of decreased uterine blood flow secondary to the increase in intra-abdominal pressure and the possible risk of CO2 absorption. Unfortunately, in a post-operative course, IUP is spontaneously aborted. In conclusion, we recommend a careful examination of the Fallopian tubes and ovaries with TVU in patients who underwent ART, even in the presence of an IUP and no abdominal pain. Declaration of interest: The authors report no conflicts of interest.
References Barrenetxea G, Barinaga-Rementeria L, de Larruzea AL et al. 2007. Heterotopic pregnancy: two cases and a comparative review. Fertility and Sterility 87: 417 e9–e15. Chin HY, Chen FP, Wang CJ et al. 2004. Heterotopic pregnancy after in vitro fertilization–embryo transfer. International Journal of Gynaecology and Obstetrics 86:411–416.
J Obstet Gynaecol Downloaded from informahealthcare.com by UMEA University Library on 04/02/15 For personal use only.
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D. I. P. Buca et al.
Figure 1. Transvaginal ultrasound examination shows. - an anechoic neoformation within yolk sac in right adnexal side (size: 9.5 ⫻ 9.8 mm); - a rounded hypoechoic mass to be referred as haematocele due to ectopic tubal pregnancy medial to left ovary (size: 22 ⫻ 23 mm); - a rounded anechoic lesion compatible with gestational sac into uterine cavity (size: 8.5 ⫻ 8.5 mm); - free fluid in the pouch of Douglas (size: 21 mm). Felekis T, Akrivis C, Tsirkas P et al. 2014. Heterotopic triplet pregnancy after in vitro fertilization with favorable outcome of the intrauterine twin pregnancy subsequent to surgical treatment of the tubal pregnancy. Case Reports in Obstetrics and Gynecology 2014:356131. Guirgis RR, Craft IL. 1991. Ectopic pregnancy resulting from gamete intrafallopian transfer and in vitro fertilization. Role of ultrasonography in diagnosis and treatment. The Journal of Reproductive Medicine 36:793–796. JOINT SOGC-CFAS 2008. Guidelines for the number of embryos to transfer following in vitro fertilization No. 182, September 2006. International Journal of Gynaecology & Obstetrics 102:203–216. Li XH, Ouyang Y, Lu GX. 2013. Value of transvaginal sonography in diagnosing heterotopic pregnancy after in-vitro fertilization with embryo transfer. Ultrasound in Obstetrics and Gynecology 41:563–569.
Pan HS, Chuang J, Chiu SF et al. 2002. Heterotopic triplet pregnancy: report of a case with bilateral tubal pregnancy and an intrauterine pregnancy. Human Reproduction 17:1363–1366. Sentilhes L, Bouet PE, Jalle T et al. 2009. Ultrasound diagnosis of spontaneous bilateral tubal pregnancy. The Australian and New Zealand Journal of Obstetrics and Gynaecology. 49:695–696. Sun SY, Araujo Júnior E, Elito Júnior J et al. 2012. Diagnosis of heterotopic pregnancy using ultrasound and magnetic resonance imaging in the first trimester of pregnancy: a case report. Case Reports in Radiology 2012: 317592. Tal J, Haddad S, Gordon N, Timor-Tritsch I. 1996. Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971 to 1993. Fertility and Sterility 66:1–12.
CASE REPORT
Early diagnosis of heterotopic triplet pregnancy with an intrauterine and bilateral tubal pregnancy after IVF: A case report
J Obstet Gynaecol Downloaded from informahealthcare.com by UMEA University Library on 04/02/15 For personal use only.
D. I. P. Buca, D. Murgano, G. Impicciatore, A. P. Castigliego, C. Iannantuono, M. Leombroni, E. Falò & M. Liberati Obstetrics and Gynecology Unit, “SS.Annunziata” Hospital Chieti, Chieti, Italy and “G. d’Annunzio” University Chieti-Pescara, Chieti, Italy DOI: 10.3109/01443615.2014.993940 Correspondence: Buca Danilo Italo Pio, Obstetrics and Gynecology Unit, G. d’Annunzio University Chieti-Pescara, Via dei Vestini, 5 66100 Chieti, Italy. Tel: 0871/358247. E-mail: [email protected]
Introduction Heterotopic pregnancy (HP) is a rare condition defined as the simultaneous presence of intrauterine pregnancy (IUP) and ectopic pregnancy (EP). It occurs in around 1/30000 of spontaneous pregnancies (Sun et al. 2012). Recently, HP has increased due to several factors: tubal damage induced by pelvic inflammatory disease (PID), previous tubal surgeries, ovarian stimulation and transfer of many embryos using assisted reproductive techniques (ART) (Felekis et al. 2014). It has increased up to 1% using ART (Chin et al. 2004; Li et al. 2013). The early diagnosis of HP is often difficult to detect because 50% of these pregnancies are asymptomatic (Sun et al. 2012). In this article, we describe a rare case of heterotopic triplet pregnancy with bilateral tubal and IUP diagnosed by trans-vaginal ultrasound (TVU) after intracytoplasmic sperm injection and embryo transfer (ICSI-ET). The objective of this article is to underline the need for an increased clinical awareness of this condition during the first-trimester TVU, even in the presence of an intrauterine gestational sac and when predisposing factors are known particularly with regard to in-vitro fertilisation (IVF).
Case report A 37-year-old Caucasian woman who had a 5-year history of idiopathic infertility underwent ICSI-ET in December 2012. In effect, at the time of treatment, three grade-A embryos were transferred 72 hours after oocytes injection (JOINT SOGC-CFAS 2008). There was no history of PID or tubal surgery and tubal patency was revealed on hysterosalpingography. Two weeks following ICSI-ET, the betahuman chorionic gonadotrophin (hCG) value was 125mIU/ml; it increased to 494mUI/ml on day 16 and to 1916mUI/ml on day 21. In this period the first TVU was performed. This examination revealed an intrauterine gestational sac and suspicious images in the fallopian tubes, in particular, on the right adnexal side, TVU revealed a round anechoic lesion with an inside yolk sac, indicative of a right tubal pregnancy. In the left adnexal area, medial to the ovary, TVU displayed a hypoechoic lesion that could be referred to as a haematocele due to a left tubal pregnancy. The endometrium appeared decidualised, and a rounded anechoic lesion was found inside the uterine cavity; this image could be referred to as a gestational sac. In the pouch of Douglas there was a fine corpuscular free fluid (Figure 1). On admission, the patient had no vaginal bleeding and no abdominal pain. We decided to perform a laparoscopic procedure and as expected, during surgery both tubal pregnancies were confirmed. Then a bilateral salpingectomy was performed. A histopathological examination confirmed the presence of
trophoblastic tissue in both the fallopian tubes. In the post-operative period, vaginal bleeding was reported and TVU revealed the spontaneous abortion of IUP. Thirty days following surgery the beta-hCG dosage was negative.
Discussion The simultaneous presence of a bilateral tubal and IUP is a rare condition and early diagnosis remains a challenge. The most important aid in the diagnosis of HP is the utilisation of high-resolution TVU. Detection of TVU is often difficult because HP maybe obscured by the presence of IUP. False negative results have been associated with markedly enlarged ovaries after ovulation induction that could mask an ectopic pregnancy (Pan et al. 2002). According to Tal et al. (1996) and Barrenetxea et al. (2007), a preoperative diagnosis is possible in a limited number of cases (41.07% and 26.25%, respectively). In contrast, Li et al. evaluating a cohort of 16483 pregnancies conceived by IVF detected 122 HPs using TVU. In particular, 72.0% of HPs were diagnosed between 5 and 6 weeks, 15.9% between 7 and 8 weeks and only 4.5% after 9 weeks (Li et al. 2013). The majority of authors recommend performing TVU at 4–6 weeks following embryo transfer (corresponding to 6–8 weeks’ gestation) (Guirgis and Craft 1991; Sentilhes et al. 2009). The present report demonstrates that an early diagnosis of simultaneous bilateral tubal pregnancy is possible using a high-resolution TVU performed on day 21 following ET (corresponding to 5 weeks’ gestation), even if an intrauterine gestational sac is already confirmed and there is no apparent risk factor. Moreover, this case suggests that adnexal sites should be assessed carefully in IVF-treated patients also in the presence of an intrauterine pregnancy. The aim of a correct early diagnosis is to evaluate the correct management of HP. The main objective is to preserve the IUP and to stop or remove the ectopic ones. The management of HP remains controversial. Surgical removal of HP offers an advantage as opposed to medical treatment (local or systemic methotrexate) or expectant management. Expectant management is possible only in selected patients with unruptured gestation and a downward trend of betahCG. Obviously, systemic methotrexate therapy is not warranted in HP because of the presence of IUP. In our particular case, because of the suspicion of a bilateral tubal pregnancy, we decided to carry out radical surgical treatment in agreement with the patient. This choice was made to reduce the risk of tubal rupture (uptrend of beta-hCG) and the resulting haemoperitoneum with hypovolemic shock. The decision to perform surgery during pregnancy must always take into consideration the potential foetal risks without compromising the safety of the mother. To preserve the IUP pregnancy, during surgery the anaesthetist prevented episodes of hypoxia and hypovolemia by monitoring the mother’s blood pressure and end-tidal CO2. In fact, during laparoscopic surgeries there are potential risks of decreased uterine blood flow secondary to the increase in intra-abdominal pressure and the possible risk of CO2 absorption. Unfortunately, in a post-operative course, IUP is spontaneously aborted. In conclusion, we recommend a careful examination of the Fallopian tubes and ovaries with TVU in patients who underwent ART, even in the presence of an IUP and no abdominal pain. Declaration of interest: The authors report no conflicts of interest.
References Barrenetxea G, Barinaga-Rementeria L, de Larruzea AL et al. 2007. Heterotopic pregnancy: two cases and a comparative review. Fertility and Sterility 87: 417 e9–e15. Chin HY, Chen FP, Wang CJ et al. 2004. Heterotopic pregnancy after in vitro fertilization–embryo transfer. International Journal of Gynaecology and Obstetrics 86:411–416.
J Obstet Gynaecol Downloaded from informahealthcare.com by UMEA University Library on 04/02/15 For personal use only.
2
D. I. P. Buca et al.
Figure 1. Transvaginal ultrasound examination shows. - an anechoic neoformation within yolk sac in right adnexal side (size: 9.5 ⫻ 9.8 mm); - a rounded hypoechoic mass to be referred as haematocele due to ectopic tubal pregnancy medial to left ovary (size: 22 ⫻ 23 mm); - a rounded anechoic lesion compatible with gestational sac into uterine cavity (size: 8.5 ⫻ 8.5 mm); - free fluid in the pouch of Douglas (size: 21 mm). Felekis T, Akrivis C, Tsirkas P et al. 2014. Heterotopic triplet pregnancy after in vitro fertilization with favorable outcome of the intrauterine twin pregnancy subsequent to surgical treatment of the tubal pregnancy. Case Reports in Obstetrics and Gynecology 2014:356131. Guirgis RR, Craft IL. 1991. Ectopic pregnancy resulting from gamete intrafallopian transfer and in vitro fertilization. Role of ultrasonography in diagnosis and treatment. The Journal of Reproductive Medicine 36:793–796. JOINT SOGC-CFAS 2008. Guidelines for the number of embryos to transfer following in vitro fertilization No. 182, September 2006. International Journal of Gynaecology & Obstetrics 102:203–216. Li XH, Ouyang Y, Lu GX. 2013. Value of transvaginal sonography in diagnosing heterotopic pregnancy after in-vitro fertilization with embryo transfer. Ultrasound in Obstetrics and Gynecology 41:563–569.
Pan HS, Chuang J, Chiu SF et al. 2002. Heterotopic triplet pregnancy: report of a case with bilateral tubal pregnancy and an intrauterine pregnancy. Human Reproduction 17:1363–1366. Sentilhes L, Bouet PE, Jalle T et al. 2009. Ultrasound diagnosis of spontaneous bilateral tubal pregnancy. The Australian and New Zealand Journal of Obstetrics and Gynaecology. 49:695–696. Sun SY, Araujo Júnior E, Elito Júnior J et al. 2012. Diagnosis of heterotopic pregnancy using ultrasound and magnetic resonance imaging in the first trimester of pregnancy: a case report. Case Reports in Radiology 2012: 317592. Tal J, Haddad S, Gordon N, Timor-Tritsch I. 1996. Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971 to 1993. Fertility and Sterility 66:1–12.
