Infertility Medications
IABLE
Medications Infertility Medications

Infertility Medications

The majority of medications commonly used in infertility treatments are not an absolute indication to pump and dump. Many of these medications may affect milk production so infant weight should be carefully monitored if treatments are started prior to one year postpartum and/or prior to significant intake of calories from other sources.

Pumping and dumping is warranted with the use of letrozole as this medication poses significant risks to the infant and is orally bioavailable to the infant – this medication should be avoided in lactating parents when possible. Clomiphene may warrant a disruption in feeding so a risk benefit discussion should be had with their physician (please section below for more details).

For more detailed information and references on specific medications, please refer to LactMed, e-lactancia, Infant Risk, or Mother to Baby.

Ovulation Stimulation

  • Clomiphene (Clomid, Milophene, Serophene): This is a selective estrogen receptor modulator commonly used to stimulate ovulation with high oral bioavailability. There is a lack of evidence on the effects of this medication on breastfed infants when taken during lactation and a lack of data on the presence of clomiphene in human milk. The high volume of distribution would make milk transfer less likely. However, due to a long half-life and high oral bioavailability, infants may still be exposed to this medication during lactation, and the risks to the infant are unknown. Additionally, its effects on the hypothalamus may suppress lactation by decreasing prolactin (1). Alternative medications should be considered and a thorough risk benefit discussion with shared decision making should be used if this medication is necessary for a lactating individual during fertility treatments.
  • Letrozole: Letrozole is an aromatase inhibitor, inhibiting estrogen synthesis and is most commonly used in hormone receptor positive breast cancer management but also to enhance fertility in those with luteal phase defects and PCOS. It is highly orally absorbed and has a long half-life of 2 days. This along with low molecular weight and low protein binding make it very likely to have significant concentration in human milk. There is no published data on its levels in human milk and it has permanent effects on estrogen inhibition so it is considered hazardous and should not be used while breastfeeding. Lactating individuals should pump and dump for the duration of treatment with this medication and for at least 10 days after completing the last dose.

Hormones and Hormone Analogues

In general, many of these hormones and hormone analogues may impact milk production but it is highly unlikely that they would be found in the breastfed child’s systemic circulation in significant quantities or affect the child. There is no absolute indication to pump and dump except for DHEA, which should be avoided in lactating individuals.

  • Choriogonadotropin alpha: (Ovitrelle, Ovidrel, Chorex, Novarel, Pregnyl, Profasi): Synthetic human chorionic gonadotropin (HCG) is used for follicular stimulation during IVF and given via intramuscular injection. This medication is a large polypeptide hormone with a large molecular weight so it would be unlikely to enter human milk. Additionally, it is not absorbed well orally. There is no absolute indication to pump and dump.
  • DHEA (Prasterone): DHEA is an adrenal hormone and precursor for androgens taken orally as a supplement with peripheral conversion to androgens (2). There is a lack of data on milk transfer of DHEA and its metabolites. Furthermore, evidence is unclear on the benefits of this medication for improving the success of in vitro fertilization (IVF) with randomized controlled trials showing no difference in outcomes (3, 4). Avoid using DHEA in lactating individuals as it does not seem to improve infertility treatment outcomes, can decrease milk production, and risks to the infant via possible exposures in breastmilk are unknown.
  • Estradiol (estradiol valerate (Progynova, Estrace, Premarin, Delestrogen), estradiol hemihydrate (Estraderm), estradiol cypionate (Depogen), estradiol (Vagifem, Femring)): Estradiol is not significantly excreted into breastmilk. Exogenous estrogens can decrease milk production, although this would be of greater concern in the initial months postpartum. There is no absolute indication to pump and dump. For more information, see the section on Contraceptives.
  • FSH (follitropin alpha or Gonal-F/Cinnal-F/Ovaleap/Bemfola) (follitropin beta or Follistim/Puregon) Urofollitropin (Bravelle, Fostimon, Metrodin, Fertinorm, Fertinex): Given via subcutaneous injection. This medication has a high molecular weight, so it is unlikely to transfer into breastmilk. Additionally, this is a glycoprotein that would be inactivated in the infant’s gut even if it does get into the milk. There is no evidence on the risk to milk production, although it does have estrogenic effects. There is no absolute indication to pump and dump.
  • Glucocorticoids (prednisolone/Orapred, prednisone, methylpredinsolone/Medrol, dexamethasone, hydrocortisone/Cortef): Glucocorticoids are naturally occurring in breast milk and may be used as an immunosuppressant in IVF at times. At high doses, glucocorticoids can cause a transient decrease in milk production. Glucocorticoids that have been more extensively studied during lactation (methylprednisolone, prednisone, prednisolone) may be preferred until more information is known. There is no absolute indication to pump and dump. For more information, see the section on Glucocorticoids in Allergy & Asthma Medications.
    • Prednisolone and prednisone have low penetration into breast milk and are not an absolute indication to pump and dump. Milk production may be suppressed with high doses of corticosteroids.
  • GnRH Agonists (buserelin/Supracur/Suprafact, leuprorelin/Lupron, nafarelin/Synarel,  goserelin/Zoladex, triptorelin/Decapeptyl/Gonapeptyl Depot/Savacyl): These subcutaneous or inhaled medications are used to inhibit FSH and LH release to suppress ovulation. They have minimal to no milk transfer and very poor oral bioavailability so they would theoretically not pose a risk to the nursing child. There is no absolute indication to pump and dump.
    • Buserelin: This medication is secreted into human milk in very small quantities but has minimal oral bioavailability. There is no absolute indication to pump and dump.
    • Luprorelin: This is a nonapeptide with unknown transfer into milk, though it likely would have minimal to no transfer based on its structure. There is no absolute indication to pump and dump.
    • Goserelin, nafarelin, gonadorelin, and triptorelin: These are LH-releasing hormone analogues and they are unlikely to enter milk or be orally bioavailable in the infant. There is no absolute indication to pump and dump.
  • GnRH Antagonists (cetrorelix/Cetrotide, ganirelix/Antagon): These can be used in place of GnRH agonists in “short protocols”. They reduce the risk of ovarian hyperstimulation. Due to their peptide structure and larger size, they are unlikely to pass into breastmilk, although studies are not available. It is also unlikely that these peptides would be stable in the child’s gastrointestinal tract, so they probably have low oral bioavailability for the infant. There is no absolute indication to pump and dump.
  • Menotrophin (Human menopausal gonadotropin (HMG)): This is used to stimulate ovulation and is administered subcutaneously or intramuscularly. Due to its high molecular weight and protein structure, it is unlikely to pass into milk and would theoretically have low to no oral bioavailability for the infant. There is no absolute indication to pump and dump.
  • Progesterone (Crinone, Cyclogest, Gestone, Utrogestan, Lubion): Low excretion into breast milk. Plasma levels are undetectable in infants of parents receiving progesterone contraceptives. There are case reports of decreased milk production with early postpartum exposure to progesterone-containing contraceptives, although decreased milk production is less likely to significantly affect a nursing toddler or older infant who is taking in other foods and drinks. There is no absolute indication to pump and dump. For more information, see the section on Contraceptives.

Other Medications Commonly Used in Infertility Management

  • Aspirin: Low dose (325 mg/day or less) aspirin is considered to be safe for breastfeeding infants or toddlers. It is occasionally used in IVF or may be used during pregnancy after fertility treatments for certain indications. Infants should be monitored for bruising and bleeding. Higher dose aspirin should be avoided during lactation due to risks of metabolic acidosis in the infant and theoretical risk of Reye’s Syndrome in the infant. While infants should be monitored for bruising or bleeding and higher doses should be avoided in the lactating parents of infants due to the theoretical risk of Reye’s Syndrome, there is no absolute indication to pump and dump.
  • Metformin: Metformin may help with cycle regulation and ovulation, especially with insulin-resistant states such as type 2 diabetes mellitus and polycystic ovarian syndrome. Metformin has minimal transfer into milk and breastfed infants’ metformin plasma levels are exceedingly low or undetectable with no known adverse effects in infants to date in the available studies. There is no absolute indication to pump and dump. For more information, see the section on Metformin under Diabetes Medications.

References

  1. Zuckerman H., S. Carmel. “The inhibition of lactation by clomiphene.” BJOG: An International Journal of Obstetrics & Gynaecology 80.9 (1973): 822-823. DOI: https://doi.org/10.1111/j.1471-0528.1973.tb11225.x.
  2. Labrie F, Bélanger A, Labrie C, et al. Bioavailability and metabolism of oral and percutaneous dehydroepiandrosterone in postmenopausal women. J Steroid Biochem Mol Biol. 2007 Oct;107(1-2):57-69. DOI: https://doi.org/10.1016/j.jsbmb.2007.02.007. Epub 2007 Jun 8.
  3. Qin JC, Fan L, Qin AP. The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis. J Gynecol Obstet Hum Reprod. 2017 Jan;46(1):1-7. DOI: https://doi.org/10.1016/j.jgyn.2016.01.002. Epub 2016 May 19.
  4. Narkwichean A, Maalouf W, Baumgarten M, et al. Efficacy of Dehydroepiandrosterone (DHEA) to overcome the effect of ovarian ageing (DITTO): A proof of principle double blinded randomized placebo controlled trial. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:39-48. DOI: https://doi.org/10.1016/j.ejogrb.2017.09.006. Epub 2017 Sep 8.