The use and misuse of opioids in the US have reached epidemic proportions and women of childbearing age may be especially affected. Many of the consequences have been well-documented, including abuse, injury, and death from overdose. However, the impact of opioids on fertility and infertility treatment is largely left out of the discussion. That must change.

To define terms, opiate refers to natural substances that come from opium that is extracted from the opium poppy. They contain chemical compounds including morphine and codeine. Opioids, on the other hand, are synthetic or semi-synthetic products that work by binding to the same receptors as opiates. Synthetic opioids include fentanyl and methadone. Oxycodone and hydrocodone are examples of semi-synthetic opioids.

Opioids and fertility

Greater awareness and education for both patients and doctors are needed on the use of opioids among women and men considering having children or undergoing infertility treatment.

The American Society for Reproductive Medicine (ASRM), the professional society of fertility specialists (reproductive endocrinologists) published a special views and reviews section on opioids and reproductive medicine in the August 2017 issue of the clinical journal Fertility and Sterility.¹ 

The goal was to address the risks of opioids to those seeking fertility care, especially women of reproductive age: those “most at risk for opioid accidents and addiction.

”In response, former ASRM President Richard J. Paulson, MD stated:

“Most reproductive medicine specialists continue to practice as if it is not a phenomenon relevant to their patients even as the epidemic has escalated.” 

He considers the special section “essential reading for all clinicians treating reproductive-age women.”

• The importance of understanding the impact of opioid use in reproductive medicine

  • • There’s a strong overlap among patient demographics for opioid use disorder and fertility treatment. In 2015, more than 40% of women between the ages of 15-44 reported they were prescribed at least one opiate prescription.²
    • Pre-conception screening revealed women were more likely to have a substance use disorder than other conditions.³
    • Long-term use or misuse of opioids affects fertility in both men and women. It may also cause sexual dysfunction, loss of libido, and depression. All of these conditions can affect the ability to get pregnant and deliver a healthy baby.

Opioid use during fertility treatment

This class of drugs is traditionally prescribed for pain relief following surgery, an acute injury, or for chronic pain. Some women who undergo surgery or other procedures to correct issues related to infertility experience significant pain for which they are prescribed opioids.

• Study: opioids after egg retrieval

Research on opioid prescription patterns following one procedure – egg retrieval for in vitro fertilization (IVF) – revealed surprising results. The study was based on a review of medical records for more than 55,000 women over an eleven-year period.

Those with a prior diagnosis of opioid or substance use disorder and women who filled more than one opioid prescription in the 12-week period before the procedure were excluded.

The researchers found an apparent “disconnect between expected procedural pain and the use of opioids:” ⁴

Although overall only 12% of women used opioids after egg retrieval. However, there was significant geographic variation:

• • • • 21% of women in the South filled a prescription
      • only 5% in the Northeast did so.

Further, women were more likely to fill an opioid prescription if they had any of the following

• • • • mood disorders
      • a history of having filled a prescription for an anti-depressant 
      • smoked cigarettes

The researchers concluded that only a small proportion of women undergoing an egg retrieval procedure fill an opioid prescription afterward. However, those who do,“receive a large quantity of opioids.” 

• A change in practice is recommended

The authors of the study suggested that since most women tolerate the procedure without opioids, “this should prompt physicians who routinely prescribe these medications to reevaluate this practice.”

Commenting on this research presented at the 2017 ASRM Scientific Congress, ASRM President Christos Coutifaris MD, Ph.D., concluded

“It is imperative that physicians treating couples with infertility not contribute to the widespread opioid abuse crisis. This kind of research raises our awareness of the potential for abuse and, hopefully, makes us cautious with our prescription patterns.”

Hopefully, the greatly increased attention to the potential dangers of opioids will alter physician prescribing patterns encouraging them to find alternatives or sharply limit the time frame for use and amount of drug prescribed.

Additional Infertility Articles from the Author:
How to Deal with Infertility and Depression
The Unique Challenges of Secondary Infertility

• Finding alternatives to opioids after surgery

It is critically important that physicians discuss alternatives to using opioids after surgery. This is because “recent data suggest that opioid exposure after other surgeries confers an increased risk for chronic opioid use” In addition, it poses at risk for relapse for those with a former opioid use disorder.

Alternatives to opioids for post-operative pain include:

• • • • nonsteroidal anti-inflammatory drugs
      • acetaminophen (e.g. Tylenol)
      • other adjunctive medications (not typically used for pain but helpful for management) 
      • regional anesthetic blocks

A variety of strategies to reduce opioid use before and after medical procedures is discussed in the following article: Perioperative Pain Management Strategies Among Women Having Reproductive Surgeries.⁵

Opioid substance use disorder and infertility

The stress of receiving a diagnosis of infertility and undergoing treatment can make patients “vulnerable to anxiety and depression, increasing their risk of developing a substance use disorder (SUD)” according to Tricia Wright, MD, MS in her 2017 paper in Fertility and Sterility.³  Further, she notes that pre-conception screening reveals,

“substance use disorders are more common than many other conditions and disorders in women trying to conceive”.

Misuse of opioids includes the following situations:

• • • continued use after the recommended time interval
    • taking the drug unrelated to any prescribed reason 
    • using a street version 

• A duty to screen patients

Dr. Wright says opioid abuse can “worsen infertility, complicate pregnancy, increase medical problems, and lead to psychosocial difficulties for the woman and her family.”

Given these serious consequences, she believes that reproductive endocrinologists have an “ethical and medical duty to screen patients” for such disorders, as well as provide initial counseling and referrals to specialized treatment.

As physicians treating women who are planning to become pregnant, she adds her colleagues are 

“well placed to help their patients avoid the consequences of SUDs (substance use disorders) in pregnancy, such as pre-term birth, low birth weight, birth defects, developmental delays, miscarriage, and neonatal abstinence syndrome.” ⁶

• Treatment of addiction in fertility patients

At the same time, some opioids – such as methadone – are used to treat addiction. If someone is on this type of drug as part of addiction treatment, they should discuss the impact on fertility with their addiction counselor and other relevant health professionals. Some treatments are less harmful to fertility than others and should be considered.

ASRM acknowledges there is little information on the treatment of opioid use disorder among the infertility population. The best approach may be to learn from the successful treatment of pregnant patients with the condition.

How do opioids affect fertility?

Research shows that opioid use affects the endocrine system. This includes the hypothalamic-pituitary axis that controls the production of sex hormones.

• Opioid-related hormonal suppression

Opioid-related hormonal suppression can lead to inappropriately low levels of gonadotropins:

• • • • follicle-stimulating hormone (FSH)
      • luteinizing hormone (LH)

There is also inadequate production of sex hormones, particularly testosterone which plays a role in male and female reproduction.

Opioids affect the female reproductive system including ovarian follicles and oocytes (immature egg cells). They may also affect the endometrium (tissue lining the uterus) and myometrium (middle layer of the uterine wall).⁷ All of these structures play a role in pregnancy.

 

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• Impact of opioids on pregnancy outcomes

Hormonal suppression may result in the following:

• • • • menstrual irregularities
      • potential problems getting pregnant
      • miscarriages 
      • pregnancy-related issues including:
        • pre-term birth,
        • low birth weight,
        • birth defects and
        • developmental delays

• Opioid impact on male reproduction

Using opioids long term can disrupt the signals controlling the production of testosterone resulting in low testosterone production. This in turn can decrease both the quantity and quality of sperm. The actual impact depends on the drug used, the dose, and the length of time it was taken.

Low testosterone also affects male libido. In one study, 20 percent of men on long-term, high dose opioids had evidence of sexual dysfunction.⁸ The researchers suggest the same may also be true for women but “evidence is scarce.”

There is no evidence that short-term use of opioids has a negative effect on male fertility. So, if the drug is taken to control pain after surgery or a broken bone, a patient should follow instructions to take only as prescribed.

Men who are taking opioids for weeks or months should talk to their doctor about cutting back. Opioid-induced hypogonadism is often a complication of long-term therapeutic use – for chronic pain or addiction – or illegal use.⁹ Experts suggest if this occurs that “nonopioid pain management, opioid rotation, or hormone supplementation” should be tried after “careful consideration of the risks and benefits.” ¹⁰

Recommendations for doctors and patients

Your fertility specialist should work with you and your partner to understand how a variety of positive and negative lifestyle habits affect your ability to get pregnant and deliver a healthy baby. The use of opioids – whether prescribed for a specific condition or because of a substance use disorder – should be discussed.

Good patient-doctor communication should be two-way. In fact, a 2015 FDA safety report on opioids urges patients to report symptoms that may be related to reproduction to their doctors,¹¹ including:

• • • lack of menstruation
    • low libido
    • erectile dysfunction 
    • infertility to their doctors

• Recommendations for doctors

Opioids are frequently prescribed for chronic pain. It is important to be cognizant of the overlap in patient demographics for misuse and fertility treatment. That being said, there are important ways to improve patient care for these patients, including: 

• • • • finding alternatives to prescribe for pain relief or addiction treatment
      • add opioid screening to patient assessment
      • monitor patients for opioid use
      • manage endocrine complications including routine screening for issues and for laboratory abnormalities in sex hormones

• Advice for patients

If you need pain relief from surgery, discuss alternatives to opioids. If treatment for opioid use disorder is needed, your physician can offer or arrange counseling – often through your fertility clinic and/or provide a referral to specialized treatment.

• • • Information for women planning a pregnancy

To address the “unique needs” of a woman planning a pregnancy who also requires treatment for opioid use disorder there are four “overlapping domains of treatment:

• • • • • • medication management,
          • medical care,
          • behavioral and mental health care, and
          • psychosocial support.”

This is discussed in more detail here: Treatments for Opioid Use Disorder Among Pregnant and Reproductive-Aged Women.¹²

The bottom line 

Undergoing treatment for infertility is challenging for patients. There are many lifestyle habits to follow or change in order to maximize your chances for success. As opioid use may affect the chances of getting pregnant and delivering a healthy baby, awareness and education should be part of the partnership between hopeful parents-to-be and their doctors.

References: 

1. Table of Contents: Views and Reviews: Special Section on Opioids and Reproductive Medicine. Fertility and Sterility, Aug. 1, 2017, vol 108, issue 2. https://www.fertstert.org/issue/S0015-0282(16)X0022-2
2. Terplan M. Women and the opioid crisis: historical context and public health solutions, Views and Reviews, Fertility and Sterility, Aug 1, 2017, vol 108, issue 2. https://www.fertstert.org/article/S0015-0282(17)30431-4/fulltext
3. Wright T, Screening, brief intervention, and referral to treatment for opioid and other substance use during infertility treatment, Views and Reviews, Fertility and Sterility, Aug. 1, 2017, vol 108, issue 2. https://www.fertstert.org/article/S0015-0282(17)30436-3/fulltext 
4. Bortoletto P, Prabhu M, Garry E, et al. Opioid prescribing patterns after egg retrieval, Fertility and Sterility, Sept. 1, 2017, vol 108, issue 3. https://www.fertstert.org/article/S0015-0282(17)30724-0/fulltext
5. Prabhu M. Bortoletto P, Bateman B. Perioperative pain management strategies among women having reproductive surgeries, Fertility and Sterility, Aug. 1, 2017, vol 108, issue 2. https://www.fertstert.org/article/S0015-0282(17)30434-X/fulltext
6. Kocherlakota P. Neonatal abstinence syndrome. Pediatrics, Aug. 2014, vol 134, issue 2.
   https://pubmed.ncbi.nlm.nih.gov/25070299/
7. Böttcher B, Seeber B, Leyendecker D, et al. Impact of the opioid systm on the reproductive axis, Fertility and Sterility, Aug. 1, 2017, vol 108, issue 2. https://www.fertstert.org/article/S0015-0282(17)30433-8/fulltext
8. Sexual dysfunction and long-term opioid use. Medical News Today, https://www.medicalnewstoday.com/articles/260580 Accessed 1/10/20
9. Male Hypogonadism. Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/male-hypogonadism/symptoms-causes/syc-20354881Accessed 1/10/20
10. Katz N, Mazar N. The Impact of Opioids on the Endocrine System, The Clinical Journal of Pain, 2009, vol 25, issue 2. https://journals.lww.com/clinicalpain/Abstract/2009/02000/The_Impact_of_Opioids_on_the_Endocrine_System.15.aspx#article-abstract-content1
11. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes, FDA, 3/22/16.  https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-several-safety-issues-opioid-pain-medicines-requires
12. Hand, D, Short V, Abatemarco V. Treatments for Opioid Use Disorder among Pregnant and Reproductive Aged Women, Fertility and Sterility, Aug. 1, 2017, Vol 108, issue 2. https://www.fertstert.org/article/S0015-0282(17)30435-1/fulltext

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Published 9/9/18. Updated by the author on 1/12/21 for republication