Repeated pregnancy losses with multiple aneuploidies and major genomic imbalance: A case report

Abstract

Rationale: If one of the partners is having balanced autosomal translocation, it is usually observed that the offspring inherit either normal chromosomes, balanced translocation identical to one of the parent or unbalanced chromosomal rearrangements of the same parental chromosome having translocation.

Concern: A unique case presented with history of 8 miscarriages for genetic counseling. The last abortus material evaluation showed monosomy of chromosome X (Turner syndrome) in all the analyzed cells. There was a history of infertility and also repeated second trimester abortions on the paternal side. On the maternal side, there was a history of intellectual disability.

Diagnose: History of repeated abnormal pregnancy outcomes. Wife’s karyotype is normal; however, husband shows translocation between chromosome 4 and 22.

Intervention: Peripheral blood sample around 3 mL was collected for karyotype. Embryo biopsy was done and DNA was extracted and processed for whole exome sequencing.

Outcomes: Wife’s karyotype is normal and husband has translocation between chromosome 4 and 22. Surprisingly, the entire pregnancy outcome including embryo screening has different, complete or partial aneuploidies of chromosomes other than chromosome 4 and 22.

Main lesson: Though the translocation in one of the parent is balanced, we have to think beyond traditional ways for evaluating a couple with repeated pregnancy loss as we cannot predict the errors at cell division. Option of in vitro fertilization and preimplantation genetic diagnosis in couples having balanced translocations should be discussed so that early intervention can prevent the agony of pregnancy loss.

Keywords

In vitro fertilization / Karyotype / Products of conception / Preimplantation genetic testing / PGT / Recurrent pregnancy loss

Conflict of interest statement

There is no conflict of interest.

Acknowledgements

We are thankful to the Director, Dr. Geetanjali Sachdeva ICMR-NIRRCH for the guidance. We are thankful to Dr. Shaini Joseph, all the GRC and NIRRCH staff for the support.

Funding

The study received financial support from ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH).

Data availability statement

The related data is made available in the manuscript.

Authors’ contributions

Shailesh Pande, Shiny Babu, and Harshavardhan Gawde contributed to development of this manuscript. Shailesh Pande conducted the genetic counseling sessions and Shiny Babu organized the sessions. Shailesh Pande and Harshavardhan Gawde were involved in analysis and Shiny Babu prepared the karyotype reports. Shailesh Pande did the interpretation of all the genetic reports. Shailesh Pande prepared the final draft of the manuscript. Neha Minde involved in documentations for Institutional Ethics Committee (IEC) approval. All authors have read and approved the final version of the manuscript for submission.

Publisher’s Note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

[1] Choi TY, Lee HM, Park WK, Jeong SY, Moon HS. Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases. Obstet Gynecol Sci 2014; 57:518-525.

[2] Bell K, Van Deerlin P, Haddad B, Feinberg R. Cytogenetic diagnosis of “normal 46, XX” karyotypes in spontaneous abortions frequently may be misleading. Fertil Steril 1999; 71(2):334-341.

[3] Bricker L, Farquharson F. Types of pregnancy loss in recurrent miscarriage: Implications for research and clinical practice. Hum Reprod 2002; 17(5):1345-1350.

[4] Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol 2007; 50:132-145.

[5] Kunwar F, Bakshi SR. Familial constitutional rearrangement of chromosomes 4 & 8: Phenotypically normal mother and abnormal progeny. J Clin Diagn Res 2016; 10:Gd01-Gd04.

[6] Ren C, Liang Y, Wei F, Zhang Y, Chen Z. Balanced translocation t(3;18) (p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism. Biochim Biophys Acta 2013; 1832(3):431-438.

[7] Sierra S, Stephenson M. Genetics of recurrent pregnancy loss. Semin Reprod Med 2006; 24:17-24.