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What would you advise for a male patient with SCD receiving HU who is concerned about teratogenicity?

October 27, 2022

November 2022

We asked, and you answered! Here are the responses from this month’s “You Make the Call” question about the potential for teratogenicity in a pregnant woman whose husband is taking hydroxyurea for sickle cell disease.


Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.


I would consider antenatal screening for any genetic or anatomical abnormalities before considering abortion, if the patient is so concerned. As was rightly said, there are no known reported cases of HU causing teratogenicity when used by male partners. I have had a few male patients on HU who have had successful, normal deliveries.

Cheryl Alexis, MD
Saint Thomas, Barbados

The results of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia by Ballas et al. in which some women became pregnant during treatment with HU showed no evidence of teratogenicity in fetuses that developed into live babies.

I would advise close monitoring of the pregnant patient using ultrasound (in first, second, and third trimesters) and would add the routine triple screen (measurements of alpha-fetoprotein, estriol, and human chorionic gonadotropin) between 15 to 20 weeks and karyotype testing performed on chorionic villus sampling between weeks 11 and 14.

I would also reassure the pregnant patient that although HU was associated with teratogenic effects in animal models, that does not seem to be the case in humans. I would make myself available to discuss with the patient as frequently as needed.

Alina Dulau-Florea, MD
Bethesda, MD

The simple answer is that teratogenicity is theoretical, if not hypothetical. If the pregnancy is advanced, an ultrasound can be done and if no major defects are seen, they could keep the pregnancy. Teratogenicity has been reported when HU is used in very high doses (3,000 times a typical therapeutic dose, for example). One dose will be metabolized by two human beings — him and his wife — and will be driven down, unlike when only a woman takes it. Again, there is no concrete evidence available that shows HU is teratogenic; it is theoretical.

George Mochamah, MSc
Nairobi, Kenya

I recommend careful clinical and biological follow-up and sonogram screening of the pregnant patient but do not advise pregnancy termination.

Samir Desai, MD
Utica, NY

I would advise the patient that there are no known data on the teratogenicity of HU in male patients whose sperm have contributed to pregnancy under natural conditions. Since HU may cause low sperm counts, the fact that his wife became pregnant suggests that the treatment is not depleting him of sperm and may not be adversely affecting sperm quality. I would advise a “wait and see” approach with more frequent examinations to detect any abnormalities in his wife’s pregnancy or the fetus, after which a more informed decision could be made about continuing the pregnancy.

Lastly, I would inform the patient that the decision to terminate his wife’s pregnancy rests with her and her pregnancy cannot be terminated on his request alone. Because his wife has a normal hemoglobin pattern and is not on any medications apart from a prenatal vitamin, it is assumed she does not have SCD. Even if she is heterozygous for the HbS mutation, the child still has a 25% chance of being born with sickle cell trait rather than SCD. Both he and his wife should consider this possibility when making their decision about continuing the pregnancy.

Katherine Wood, PhD
Pittsburgh, PA

I would advise them not to terminate the pregnancy. Most study results show that HU affects sperms count, motility, and morphology in human males and that some effects are even reversible upon cessation of HU, but no teratogenic effect was reported in males taking HU.

My experience is that an unplanned pregnancy while on HU yields no teratogenic effect and most pregnancy complications are due to the disease itself. I often advise female patients to stop HU six months before pregnancy and don’t recommend termination if they get pregnant.

Heba Ibrahim, PhD Candidate
Cairo, Egypt

The evidence provided in a 2021 study by Ware et al. does not suggest there is a risk if the male partner was using HU. The evidence indicates HU lowers sperm count, but if the wife is pregnant, I do not believe it is necessary to terminate the pregnancy, except if there is concern about medical-legal issues.

Deborah Rund, MD
Jerusalem, Israel

This is a complex area to counsel patients. Firstly, this is an established pregnancy, hence the discussion is very different to pre-pregnancy counselling. It is also the patient’s partner who is pregnant, so I would arrange to meet with them together. Assuming such a conversation can be arranged, I would conduct the counselling with the following principles in mind:

  • Affirm and validate the fears regarding potential sperm abnormality and reassure that my aim is to help and support them in their decision. I would then ask their permission to present them with some perspectives on the situation to aid the discussion.
  • Explain the background risk of any pregnancy despite optimal circumstances. This would be of a magnitude greater than any increase engendered by HU use.
  • Explain that our knowledge base is less than we would like but that there is cohort data of males taking HU at time of conception with no evidence of increased fetal abnormality.
  • HU has been associated with low sperm count in animal studies, but this seems to not be of great effect in humans. From first principles it is likely that surviving and motile sperm have an intact genetic message.

Overall, it is probable that the risks of proceeding with the pregnancy would only be marginally increased over and above the normal background pregnancy risks.

I would give them time to consider the information and return after a few days to discuss further.

John Hounsell, MBBS
Warrnambool, Australia

I hear your concern. HU results in low sperm count and possible teratogenicity in pregnant female patients. However, no reliable data for teratogenicity in a pregnant female partner of a male patient are available. That said, I would advise close follow-up with clinical and ultrasonographic examinations.

Israr Khan, MD
Fairview, New Jersey

 

 

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