IVF versus metropole for Dry Eye Disease symptoms

In vitro fertilization (IVF) appears more likely to worsen dry eye than letrozole, based on available evidence showing that IVF causes significant increases in dry eye symptoms and tear film alterations, while letrozole's hormonal effects may actually be protective for the ocular surface. According to the literature, IVF does have more risks, but usually that risk is manageable with the treatments we provide at the office such as Preservative free, autologous – meaning it comes from your own body PRP eye drops and amniotic membrane if the usual FDA approved anti-inflammatory eye drops like lifitegrast Xiidra or cyclosporine (Restasis, Vevye, Cequa) do not help.

IVF treatment results in dramatic elevations of serum estrogen (10-50 times baseline levels) that are associated with worsening dry eye symptoms and ocular pain, as well as decreased tear breakup time and tear secretion.[1] In a study of 40 women undergoing IVF, dry eye symptoms significantly worsened (p [1] Higher estradiol levels and lower luteinizing hormone were associated with worsening dry eye symptoms during IVF cycles.[1]  

In contrast, letrozole—an aromatase inhibitor sometimes used as co-treatment during ovarian stimulation—markedly suppresses estradiol levels (by 58-68% during the follicular phase) while increasing androgen levels including testosterone and androstenedione.[2][3] This hormonal profile may be protective, as dry eye disease is more strongly associated with low androgen levels than with either high or low estrogen levels.[4] Androgens have beneficial effects on meibomian gland secretions and are expressed throughout ocular tissues.[4]  

  

FDA labeling for letrozole lists eye irritation, blurred vision, and cataracts among reported adverse effects, but dry eye is not specifically mentioned as a common side effect.[5][6] A comprehensive real-world safety analysis of 29,631 letrozole cases in the FAERS database did not identify dry eye as a significant adverse drug reaction signal.[7]  

  

No direct comparative studies exist examining dry eye outcomes between IVF and letrozole treatment, limiting definitive conclusions. However, the available evidence suggests IVF's supraphysiological estrogen elevation transiently worsens dry eye, while letrozole's estrogen-lowering and androgen-increasing effects would theoretically be less likely to exacerbate—and might even ameliorate—dry eye symptoms.  

  

---  

  

Full Citation References:  

  

 Boga A, Stapleton F, Chapman M, Golebiowski B.[1] Effects of Elevated Serum Estrogen on Dry Eye in Women Undergoing in Vitro Fertilisation. The Ocular Surface. 2023;29:511-520. doi:10.1016/j.jtos.2023.06.015. PMID: 37422153.  

  

 Clayton JA.[4] Dry Eye. The New England Journal of Medicine. 2018;378(23):2212-2223. doi:10.1056/NEJMra1407936.  

  

 Bülow NS, Skouby SO, Warzecha AK, et al.[2] Impact of Letrozole Co-Treatment During Ovarian Stimulation With Gonadotrophins for IVF: A Multicentre, Randomized, Double-Blinded Placebo-Controlled Trial. Human Reproduction (Oxford, England). 2022;37(2):309-321. doi:10.1093/humrep/deab249. PMID: 34792133.  

  

 Poulsen LC, Warzecha AK, Bülow NS, et al.[3] Effects of Letrozole Cotreatment on Endocrinology and Follicle Development in Women Undergoing Ovarian Stimulation in an Antagonist Protocol. Human Reproduction (Oxford, England). 2022;37(7):1557-1571. doi:10.1093/humrep/deac119. PMID: 35652260.  

  

 Food and Drug Administration.[5] LETROZOLE. 2016. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=968611f1-ef03-47a6-8dae-4834f77d23bd  

  

 Food and Drug Administration.[6] Letrozole. 2025. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32d7dd83-a3ef-41fe-e063-6394a90ae62a  

  

 Liang C, Zhang Y, An P, Zuo W, Zhang B.[7] Safety Profile of Letrozole in the Real World: A Disproportionality Analysis of FAERS Database and Systematic Review of Case Reports. Expert Opinion on Drug Safety. 2025. doi:10.1080/14740338.2025.2527964. PMID: 40590361.  

  

  

Would you like me to review whether any studies have evaluated long-term ocular surface outcomes or persistent dry eye symptoms following IVF or letrozole treatment, to better understand if these effects are transient or could have lasting clinical significance?  

  

References

1. Effects of Elevated Serum Estrogen on Dry Eye in Women Undergoing in Vitro Fertilisation. Boga A, Stapleton F, Chapman M, Golebiowski B. The Ocular Surface. 2023;29:511-520. doi:10.1016/j.jtos.2023.06.015.

2. Impact of Letrozole Co-Treatment During Ovarian Stimulation With Gonadotrophins for IVF: A Multicentre, Randomized, Double-Blinded Placebo-Controlled Trial. Bülow NS, Skouby SO, Warzecha AK, et al. Human Reproduction (Oxford, England). 2022;37(2):309-321. doi:10.1093/humrep/deab249.

3. Effects of Letrozole Cotreatment on Endocrinology and Follicle Development in Women Undergoing Ovarian Stimulation in an Antagonist Protocol. Poulsen LC, Warzecha AK, Bülow NS, et al. Human Reproduction (Oxford, England). 2022;37(7):1557-1571. doi:10.1093/humrep/deac119.

4. Dry Eye. Clayton JA. The New England Journal of Medicine. 2018;378(23):2212-2223. doi:10.1056/NEJMra1407936.

5. LETROZOLE. Food and Drug Administration. Updated date: 2016-04-01.

6. Letrozole. Food and Drug Administration. Updated date: 2025-04-15.

7. Safety Profile of Letrozole in the Real World: A Disproportionality Analysis of FAERS Database and Systematic Review of Case Reports. Liang C, Zhang Y, An P, Zuo W, Zhang B. Expert Opinion on Drug Safety. 2025;:1-11. doi:10.1080/14740338.2025.2527964.