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. 2015 Sep 9;9(9-10):E667–E670. doi: 10.5489/cuaj.2902

Reproductive outcomes in men with karyotype abnormalities: Case report and review of the literature

Taylor P Kohn *, Raul Clavijo †, Ranjith Ramasamy *, Tariq Hakky *, Aravind Candrashekar *, Dolores J Lamb *, Larry I Lipshultz *,✉
PMCID: PMC4581942  PMID: 26425238

Abstract

Reciprocal translocations of autosomal chromosomes are present in about 1/625 men, yet often there are no symptoms except primary infertility. Abnormal segregation during meiosis often produces sperm and subsequent embryos with unbalanced translocations that often ultimately result in spontaneous abortions. We report on a 37-year-old man and his 39-year-old wife who complained of primary infertility. Previous in vitro fertilization (IVF) had resulted in pregnancy, but two spontaneous abortions. Upon chromosomal testing, the man was diagnosed with a reciprocal translocation and his wife was diagnosed with mosaic Turner’s syndrome. Through testicular sperm extraction (TESE) and IVF with preimplantation genetic screening (PGS), they succeeded in having two healthy children. Since men with different karyotype abnormalities can have male infertility, we reviewed the literature and summarized the reproductive outcomes for men with both autosome and sex chromosomal karyotype abnormalities.

Case report

A 37-year-old man and his 39-year-old wife presented due to a complaint of primary infertility. They had been trying to conceive for 12 years. Two years previously, the patient had undergone bilateral testicular biopsies with successful sperm retrieval and conception. Unfortunately, the couple experienced recurrent pregnancy loss (both during first trimester) following two cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) without genetic testing. On examination, the man had bilaterally descended testis with a right testicular size of 18 cc and a left testicle size of 16 cc. No varicocele was palpable; the vas deferens and epididymis were palpable bilaterally. Testosterone levels were 241 ng/dL, follicle stimulating hormone levels 7 mIU/mL, and luteinizing hormone levels were 5 mIU/mL. Semen analysis revealed no sperm. Based on the evaluation and previous operation at the outside institution, the patient was diagnosed with azoospermia likely secondary to epididymal obstruction.

The couple was sent for genetic evaluation due to recurrent pregnancy loss. Genetic evaluation showed that the husband had a reciprocal translocation involving chromosomes 4 and 8 [46,XY;t(4;8)(q31.1;q22.3)]. In addition, his wife had 45,X/46,XX mosaicism. The patient underwent a successful right testicular sperm extraction (TESE) with IVF/ICSI combined with pre-implantation genetic screening (PGS). The result was a successful live birth. Two years later, a repeat TESE was performed for another IVF/ICSI/PGS cycle, and the couple had a second healthy child.

Discussion

The prevalence of reciprocal translocations in the general population is about 1/625.1 This prevalence is greater in infertile couples (1/166), in couples who have failed to achieve a pregnancy after >10 total embryos transferred for IVF (1/31), and in couples who have experienced ≥3 consecutive first-trimester spontaneous abortions (1/11).2 Studies have shown that for couples in whom the male has a reciprocal translocation, 75% of natural pregnancies will result in a spontaneous abortion, with a live birth rate of only 4.9%.3,4 Increased frequency of male infertility in men with reciprocal translocations is due to abnormal meiosis during spermatogenesis.5 Abnormal segregation during meiosis can result in sperm with unbalanced translocations (i.e., chromosomal duplications and deletions).6 Embryos with unbalanced translocations are at a high risk of spontaneous abortion, stillbirth, or neonatal anomalies, and only 11.5% experience births of healthy infants. This explains why couples with a reciprocal translocation have significant problems conceiving and carrying to term.7

In recent years, preimplantation genetic screening (PGS) has significantly improved the frequency of healthy births in couples with genetic abnormalities. Screening the embryo prior to implantation assures that only those embryos with appropriate numbers of chromosomes are implanted. For couples in whom one or more partners have a reciprocal translocation, preimplantation genetic diagnosis (PGD) reduced the frequency of spontaneous abortions to 12.5% and increased the live birth rate to more than 80%.3,4

Due to the complexity of translocations and the high incidence of chromosomal aneuploidy with similar phenotypes, a review of the existing literature was critical (Table 1). Most patients with chromosomal abnormalities, with the notable exception of patients with 45,X/46,XY including those with complex chromosomal rearrangements, can still achieve pregnancies. This literature review reveals that sperm retrieval appears necessary in the presence of many sex chromosomal abnormalities, whereas patients with autosomal chromosomal abnormalities are often oligospermic and thus do not require testicular sperm extraction. Further, it appears that for patients with sex chromosomal abnormalities, including those with Kleinfelter syndrome, sperm retrieval combined with assisted fertility treatment offers a good prognosis for pregnancy.

Table 1.

Summary of literature pertaining to sperm retrieval in patients with autosomal and sex chromosome abnormalities

Study Age Year Karyotype abnormality No. cases Semen analysis Sperm retrieval Assisted Fertility Pregnancy
Autosomal chromosome abnormality
Current case 42 2015 46,XY,t(4;8)(q31.1;q22.3) 1 Azoospermia Yes Yes Yes
Ananthapur et al.8 34 2013 46, XY, t (2;11) (p14;q21) 1 Oligospermia No No Yes (3)
Almeida et al.9 31 2012 46,XY,t(2;2)(p25.1;q23) 1 Oligoasthenozoospermia No No Yes
Motoyama et al.10 28 2011 46,XY, t(10; 21)(q11.2; p11.2) 1 Oligoasthenozoospermia Yes Yes Yes
Joly-Helas et al.11 35 2007 46,XY,t(4;11)(q34;q13.5) 1 Oligospermia No Yes Yes
Drouineaud et al.12 34 2003 45,XY, der(13;14),(q10;q10) 1 Azoospermia Yes Yes Yes
Cai et al.13 35 2000 46,XY,t(7;9)(q22;p24),ins(8;7) (q21.2;q22q32).ish der(9) (wcp7+);ins(8;7) (wcp8+,wcp7+) 1 Oligospermia No No Yes
Belin et al.14 NA 1999 46,XY,t(20;22)(q12.0;q11.21) 1 Oligospermia NA Yes Yes
Meschede et al.15 NA 1997 46,XY,t(1;9)(q44;p11.2) 1 Oligospermia NA Yes Yes
Veld et al.16 41, NA 1997 45,XY,der(13;13)(q10; q10)/46,XY,t(13;13)(p10;p10), der(13p;13p) AND 45,XY,der(13;14)(q10;q10) 2 Oligospermia No Yes Yes
Sex chromosome abnormality
Flannigan RK et al.17 27 2014 45,X/46,XY 1 Azoospermia Yes Yes No
Abdel-Razic et al.18 23–40 2011 47,XYY 9 Oligospermia (7)
Azoospermia (2)		 No Yes (2) Yes (1)
Kilic et al.19 25–32 2010 45,X/46,XY 3 Azoospermia (2)
Oligospermia (1)		 Yes (2) Yes (1) No
Spinner et al.20 NA 2008 46,Xr(Y) 1 Oligospermia Yes Yes Yes
Sugawara et al.21 27 2005 46, XX/46, XY 1 Azoospermia Yes Yes Yes
Kleinfelter syndrome
Sabbaghian et al.22 32 (mean) 2014 47, XXY 134 Azoospermia Yes (38) Yes (18) Yes (4)
Greco et al.23 35 (mean) 2013 47,XXY 38 Azoospermia Yes (15) Yes (11) Yes (11)
Vicdan et al.24 35 2011 47, XXY 1 Azoospermia Yes Yes Yes
Ramasamy et al.25 33 (mean) 2009 47,XXY 68 Azoospermia Yes (45) Yes (45) Yes (33)
Yarali et al.26 32 (mean) 2009 47,XXY 33 Azoospermia Yes (22) Yes (22) Yes (7)
Kyono et al.27 30 (mean 2)
38 (mean 1)		 2007 47,XXY 17 Azoospermia Yes (6) Yes (6) Yes (5)
Koga et al.28 36 (mean) 2007 47,XXY 26 Azoospermia Yes (13) Yes (13) Yes (3)
Schiff et al.29 24–52 2005 47,XXY (39) AND 46,XX/47,XXY(3) 42 Azoospermia Yes (29) Yes (29) Yes (18)
Okada et al.30 25–43 2005 47,XXY 51 Azoospermia Yes (26) Yes (26) Yes (12)
Seo et al.31 26–42 2004 47,XXY (25) AND 46,XY/47,XXY(11) 36 Azoospermia Yes (10) Yes (10) Yes (4)
Vernaeve et al.32 29.5 (mean) 2004 47,XXY 50 Azoospermia Yes (24) NA NA
Westlander et al.33 33 (mean) 2003 47,XXY 18 Azoospermia Yes (5) Yes (5) Yes (2)
Yamamoto et al.34 NA 2002 47,XXY 24 Azoospermia Yes (12) Yes (12) Yes (4)
Friedler et al.35 28.7 (mean) 2001 47,XXY 12 Azoospermia Yes (5) Yes (5) Yes (5)
Cruger et al.36 28 2001 47,XXY 1 Oligospermia No Yes Yes
Poulakis et al.37 33,35 2001 47,XXY 2 Azoospermia Yes Yes Yes
Levron et al.38 NA 2000 47,XXY 20 Azoospermia Yes (8) Yes (8) Yes (4)
Ron-El et al.39 31 2000 47,XXY 1 Azoospermia Yes Yes Yes
Nodar et al.40 39 1999 47,XXY 1 Azoospermia Yes Yes Yes
Tourmaye et al.41 NA 1997 47,XXY 15 Azoospermia Yes (8) Yes (7) Yes (2)
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While in this case report the IVF/ICSI attempts resulted with two healthy, live births, there is an ethical concern that an abnormal karyotype might be passed onto the prodigy. In countries where the law does not preclude assisted reproductive techniques for couples with a balanced chromosomal translocations, the couple ought to be referred to genetic counselling and be advised that an abnormal karyotype might be passed onto the prodigy before starting assisted reproductive techniques.

Conclusion

We report a successful pregnancy using TESE and IVF/ICSI in a couple in whom both individuals had abnormal karyotypes. The use of sperm extraction techniques and assisted fertility treatments, including pre-implantation genetic screening, dramatically helped these patients with chromosomal abnormalities achieve viable pregnancies. We expect genetic defects in men with infertility will be diagnosed with greater precision (beyond translocation) since molecular diagnostics, such as next-generation sequencing and microarray-based comparative genomic hybridization (array-CGH) analysis, have now been incorporated into clinical labs.

Footnotes

Competing interests: The authors all declare no competing financial or personal interests.

This paper has been peer-reviewed.

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