How Could One Sperm and One Oocyte Proceed To Molar Pregnancy? Prevalence of Molar Pregnancy during ICSI Procedure in Over 25,000 Fresh Embryo Transfers: A Retrospective Cross-Sectional Study

Document Type : Original Article


1 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

2 School of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


Background: Gestational trophoblastic disease (GTD) is a heterogeneous group of diseases characterized by excessive proliferating trophoblastic tissue. The prevalence of GTD has a varied geographical distribution. However, its frequency following intracytoplasmic sperm injection (ICSI) cycles has not yet been reported. This study aimed to estimate GTD frequency and prevalence after ICSI cycles.
Materials and Methods: This retrospective cross-sectional study included all patients diagnosed with GTD subsequent to ICSI and segmental embryo transfer procedure during 2011-2019 at Royan Institute. GTD diagnosis was established for patients who met all three criteria: beta-human chorionic gonadotropin (β-hCG) levels greater than 100,000 mIU/mL, vesicular ultrasonographic pattern, and presence of pathologic features of hydatidiform mole. Although we assessed the GTD frequency in all ICSI cycles, GTD cases were only observed following fresh embryo transfer ICSI procedures.
Results: We evaluated 25,667 fresh embryo transfer ICSI procedures out of 41,540 ICSI cycles. This study identified a total of 10 GTDs confirmed by all criteria which were mentioned previously. Of these 10 GTDs, nine cases had hydatidiform mole, and one had gestational trophoblastic neoplasia. The frequency of GTD was calculated 10 cases in 41,540 (0.240 per 1000) ICSI procedures and 10 in 25,667 (0.389 per 1000) fresh embryo transfers following ICSI cycles. Also, we detected 10 GTD cases in 8,196 (1.220 per 1000) clinical pregnancies.
Conclusion: We discuss that the possibility of GTD after ICSI procedure is not as low as expected. Thus, the previous theses are insufficient to explain all aspects of molar pregnancy, and more research is required.


Main Subjects

  1. Kaur B. Pathology of gestational trophoblastic disease (GTD). Best Pract Res Clin Obstet Gynaecol. 2021; 74: 3-28.
  2. Santaballa A, García Y, Herrero A, Laínez N, Fuentes J, De Juan A, et al. SEOM clinical guidelines in gestational trophoblastic disease (2017). Clin Transl Oncol. 2018; 20(1): 38-46.
  3. Candelier JJ. The hydatidiform mole. Cell Adh Migr. 2016; 10(1-2): 226-235.
  4. Hui P, Ronnett BM. Hydatidiform moles: genetic basis and precision diagnosis. Annu Rev Pathol. 2017; 12: 449-485.
  5. Kaur B, Sebire NJ. Gestational trophoblastic tumours and non-neoplastic trophoblastic lesions: morphology and immunocytochemistry to refine the diagnosis. Diagn Histopathol. 2019; 25(2): 53-65.
  6. Petignat P, Senn A, Hohlfeld P, Blant SA, Laurini R, Germond M. Molar pregnancy with a coexistent fetus after intracytoplasmic sperm injection. A case report. J Reprod Med. 2001; 46(3): 270-274.
  7. Savage P, Sebire N, Dalton T, Carby A, Seckl MJ, Fisher RA. Partial molar pregnancy after intracytoplasmic sperm injection occurring as a result of diploid sperm usage. J Assist Reprod Genet. 2013; 30(6): 761-764.
  8. Wood SJ, Sephton V, Searle T, Troup S, Kingsland C. Partial hydatidiform mole following intracytoplasmic sperm injection and assisted zona hatching. BJOG. 2002; 109(8): 964-966.
  9. Fisher RA, Maher GJ. Genetics of gestational trophoblastic disease. Best Pract Res Clin Obstet Gynaecol. 2021; 74: 29-41.
  10. Yamada T, Matsuda T, Kudo M, Yamada T, Moriwaki M, Nishi S, et al. Complete hydatidiform mole with coexisting dichorionic diamniotic twins following testicular sperm extraction and intracytoplasmic sperm injection. J Obstet Gynaecol Res. 2008; 34(1): 121-124.
  11. World Health Organization. Gestational trophoblastic diseases: report of a WHO scientific group [ meeting held in Geneva from 6 to 10 December 1982]. Geneva: World Health Organization; 1983. Available from: (18 May 2021).
  12. Parker VL, Tidy JA. Current management of gestational trophoblastic disease. Obstet Gynaecol Reprod Med. 2017; 27(11): 338-345.
  13. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010; 203(6): 531-539.
  14. Javey H, Sajadi H. II. Hydatidiform mole in Southern Iran: a statistical survey of 113 cases. Int J Gynaecol Obstet. 1978; 15(5): 390-395.
  15. Almasi A, Almassinokiani F, Akbari P. Frequency of molar pregnancies in health care centers of Tehran, Iran. J Reprod Infertil. 2014; 15(3): 157-160.
  16. Ulug U, Ciray NH, Tuzlali P, Bahçeci M. Case report: partial hydatidiformmole following the transfer of single frozen–thawed embryo subsequent to ICSI. Reprod Biomed Online. 2004; 9(4): 442-446.
  17. Makhseed M, Al-Sharhan M, Egbase P, Al-Essa M, Grudzinskas J. Maternal and perinatal outcomes of multiple pregnancy following IVF-ET. Int J Gynaecol Obstet. 1998; 61(2): 155-163.
  18. Olesnicky G, Quinn M. Molar pregnancy after artificial insemination (donor). The Lancet. 1984; 323(8389): 1296.
  19. May J, Stark Z, Thomas P. Partial hydatidiform mole following intracytoplasmic sperm injection and transfer of a cryopreserved-thawed blastocyst. J Obstet Gynaecol. 2015; 35(3): 320-321.
  20. Pan Z, Usui H, Sato A, Shozu M. Complete hydatidiform moles are composed of paternal chromosomes and maternal mitochondria. Mitochondrial DNA A DNA Mapp Seq Anal. 2018; 29(6): 943-950.
  21. Hafezi M, Chekini Z, Zamanian MR. Which is more prominent in recurrent hydatidiform mole, ovum or sperm? Int J Fertil Steril. 2020; 14(2): 154-158.
  22. Eagles N, Sebire N, Short D, Savage P, Seckl M, Fisher R. Risk of recurrent molar pregnancies following complete and partial hydatidiform moles. Hum Reprod. 2015; 30(9): 2055-2063.
  23. Mohammadali F, Pourfathollah A. Association of ABO and Rh blood groups to blood-borne infections among blood donors in Tehran-Iran. Iran J Public Health. 2014; 43(7): 981-989.
  24. Jagtap SV, Aher V, Gadhiya S, Jagtap SS. Gestational trophoblastic disease-Clinicopathological study at tertiary care hospital. J Clin Diagn Res. 2017; 11(8): EC27-EC30.