Can medications for In Vitro Fertilization (IVF) cause macrocytosis?

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From the Guidelines

Medications used in In Vitro Fertilization (IVF) can cause macrocytosis, particularly those that interfere with folate metabolism, such as methotrexate and certain folate antagonists. When considering the potential for macrocytosis in IVF patients, it's crucial to examine the effects of various medications on folate levels and red blood cell production.

  • Methotrexate, for instance, is known to inhibit dihydrofolate reductase, an enzyme essential for folate metabolism, and can lead to macrocytosis 1.
  • Other medications like azathioprine and 6-mercaptopurine can also induce macrocytosis, but through myelosuppressive activity rather than direct interference with folate metabolism 1.
  • The use of folate antagonists in some fertility medications may further contribute to the development of macrocytosis.
  • Clomiphene citrate and gonadotropins, commonly used in IVF, do not directly cause macrocytosis but may influence red blood cell production through hormonal changes.
  • Regular blood monitoring during IVF treatment is vital for early detection of macrocytosis, allowing for timely adjustments to medication regimens or the addition of folate supplementation as needed.
  • The ECCO-ESPGHAN guidelines recommend oral administration of folate in patients on methotrexate, which could be applicable to IVF patients undergoing treatment with similar medications 1.

From the Research

Causes of Macrocytosis

  • Macrocytosis can be caused by various factors, including vitamin B12 and folate deficiencies, alcoholism, liver disease, hypothyroidism, and certain medications 2, 3, 4.
  • The most common etiologies of macrocytosis are vitamin B12 and folate deficiencies, which can be preventable 3.
  • Other possible causes of macrocytosis include primary bone marrow dysplasias, such as myelodysplastic syndrome and myeloproliferative disorders 2, 5.

Medications and Macrocytosis

  • Certain medications can cause macrocytosis, although the specific medications are not mentioned in the provided studies 2, 4.
  • It is not explicitly stated in the provided studies whether medications for In Vitro Fertilization (IVF) can cause macrocytosis.
  • However, it is known that certain medications can interfere with folate and vitamin B12 metabolism, potentially leading to macrocytosis 6, 4.

Diagnosis and Evaluation of Macrocytosis

  • The diagnosis of macrocytosis typically involves a complete blood count, peripheral blood film, and serum vitamin B12 and folate levels 3, 4.
  • A reticulocyte count and liver function tests may also be helpful in evaluating the underlying cause of macrocytosis 2, 5.
  • In some cases, a bone marrow biopsy may be necessary to establish a diagnosis of a primary bone marrow disorder 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of macrocytosis.

American family physician, 2009

Research

Diagnosis and treatment of macrocytic anemias in adults.

Journal of general and family medicine, 2017

Research

Unexplained macrocytosis.

Southern medical journal, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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