Psychedelics & Infertility
Written by Lindsey Block
Inevitably women will reach a point when they can no longer become pregnant; however, the age at which fertility success begins to decline varies [1]. At the peak time in which pregnancy can occur, recurrent intercourse results in approximately 52% successful pregnancy in females aged 19 - 26 years old and 30% in females ages 35-39 years old. Interestingly and not widely divulged, male semen parameters decline around the age of 35 and their fertility generally decreases after the age of 50. Success of pregnancy peaks in the first few months with 80% of couples conceiving within the first 6 months. At the peak time of pregnancy success, the probability of getting pregnant from a single-act of intercourse is approximately 9%.
In the US, about 15% of couples with infertility do not have an identifiable cause. 25% of infertility diagnoses are due to ovulatory disorders [2]. Anovulation is suspected if menstrual cycles are irregular, less than 21 days or longer than 35 days, lack of a period, or abnormal uterine bleeding [2]. Polycystic ovarian syndrome (PCOS) impacts 70% of women who experience anovulation, or lack of egg release. Other causes of anovulation include obesity, thyroid disease (2-3%), pituitary disease (13%), high androgen levels (2%), being underweight, and having an eating disorder. In addition to ovulatory dysfunction, other prominent causes of infertility include tubal occlusion, endometriosis, insufficient ovarian reserves, uterine factors and male factors. Male factors impact approximately 1 in 3 couples experiencing infertility [2]. These factors include low testosterone and low sperm count, which can occur due to an obstruction [2, 3]. Lifestyle factors that can impact fertility include weight, diet, and tobacco consumption [1, 2]. A negative association was found between male consumption of alcohol, caffeine, and red meat and pregnancy [2]. Interestingly, infertility is associated with increased risk of cancer in males and females. No association with cancer and fertility treatments was found. Environmental toxins and pollutants also can reduce fertility in both males and females [1].
People, particularly women, who experience infertility and fertility issues report increased rates of depression and anxiety [4]. However, the effect of stress on fertility is less understood. Studies found that 30 - 76% of women experiencing fertility issues experienced depression, anxiety, or both. Drugs used to treat infertility can result in psychological symptom onset and development as well. In addition, patients with failed treatment report significantly greater depression and anxiety, which increases with increased failed treatment attempts. Psychological stress also can hinder women from pursuing treatment or preemptively stopping treatment. Studies on the impact of stress pre- and during treatment are inconclusive, potentially due to inconsistencies/ inaccuracies in self-reports.
Furthermore, drugs currently licensed for the treatment of anxiety and depression have their own warning for use whilst trying to conceive, as well as causing a reduction in fertility in females and males [5-10]. In addition, data suggest the use of antidepressants during pregnancy can negatively impact fetal development and increase the risk of miscarriage and preterm labor [11]. The potential reproductive harm of antidepressants and anti-anxiety are not well understood, in part due to the 1977 United States FDA guidelines that inhibited most females of reproductive age being able to partake in clinical research. It was not until 1993 that the US Congress passed the NIH Revitalization Act, which pushes for inclusion of females in clinical research. More studies are needed to determine the true effect of antidepressant and antianxiety medications on fertility as well as the direct effect of depression and anxiety on fertility.
Psychedelics have been shown to reduce markers of stress and immune response [12], as well as reduce depression and anxiety [13, 14] as psychedelics allow for psychological insight and reductions in experiential avoidance [15], allowing people to come to terms with the struggle and reality of being infertile.
The stress-infertility cycle
Could psychedelic treatment pre infertility treatment increase fertility treatment success? Could psychedelic treatment decrease the need for fertility treatments? Can psychedelic treatment post infertility trials, once the couple no longer wants to pursue infertility treatment, be an important step towards helping the couple overcome the disappointment?
Single use of psychedelics to improve depression and anxiety can have a long lasting, maintained effect [16] without the continued use of any medication. Psychedelic medicine may be a better option for depression, anxieties, and stress in someone wanting to get pregnant, so that they do not have to choose between getting treatment and taking daily medication. Not only can psychedelics impact mental states, but they can influence body physiology.
Ketamine has been shown to be a potent antidepressant with one dose lasting an average of 7 days in patients who do not experience relief from other antidepressants [17].
Questions for the field
Do psychedelics impact blood flow? Could altered blood flow impact reproductive tissue health?
While some evidence indicates that psychedelics may influence cerebral blood flow [18], the existing literature does not offer conclusive evidence on their impact on blood flow in other regions of the body. Therefore, further research is needed to comprehensively understand the effects of psychedelics on systemic blood flow.
How long do psychedelics remain in the blood? Can these chemicals be taken up by gametes (eggs and sperm)?
Psilocybin, lysergic acid diethylamide (LSD), and ketamine are not detectable in plasma sample 24 hours post dosage [17, 19, 20]. The plasma half-life of 3,4-methylenedioxymethamphetamine (MDMA) is ~ 6-8 hours [21]. Although the quantities of these drugs and the pharmacokinetics of their metabolites are noted, the impact these metabolites can have on the body require more study. A review of LSD found no association between chromosomal abnormalities and LSD intake, although the potential effects of LSD on fetal development is unclear [22].
Conclusion
There are limited and conflicting options for those experiencing infertility and depression or anxiety. Currently, people need to weigh the pros and cons of getting infertility treatment with their mental health treatment. However, there are additional options out there. Psychedelic treatment has potential to help people better manage their mental health prior to starting infertility treatments. In addition, psychedelics may help people overcome the devastation often felt after failed infertility treatments.
References
Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive E, Infertility. Electronic address Aao, Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive E, Infertility. Optimizing natural fertility: a committee opinion. Fertil Steril 2017; 107:52-58.
Carson SA, Kallen AN. Diagnosis and Management of Infertility: A Review. JAMA 2021; 326:65-76.
Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol 2018; 15:369-384.
Rooney KL, Domar AD. The relationship between stress and infertility. Dialogues Clin Neurosci 2018; 20:41-47.
Casilla-Lennon MM, Meltzer-Brody S, Steiner AZ. The effect of antidepressants on fertility. Am J Obstet Gynecol 2016; 215:314 e311-315.
Evans-Hoeker EA, Eisenberg E, Diamond MP, Legro RS, Alvero R, Coutifaris C, Casson PR, Christman GM, Hansen KR, Zhang H, Santoro N, Steiner AZ, et al. Major depression, antidepressant use, and male and female fertility. Fertil Steril 2018; 109:879-887.
Gok S, Gok BC, Alatas E, Senol H, Topak OZ. Effects of Selective Serotonin Reuptake Inhibitor Treatment on Ovarian Reserves in Patients with Depression. Medicina (Kaunas) 2023; 59.
Beeder LA, Samplaski MK. Effect of antidepressant medications on semen parameters and male fertility. Int J Urol 2020; 27:39-46.
Milosavljevic JZ, Milosavljevic MN, Arsenijevic PS, Milentijevic MN, Stefanovic SM. The effects of selective serotonin reuptake inhibitors on male and female fertility: a brief literature review. Int J Psychiatry Clin Pract 2022; 26:43-49.
Domar AD, Moragianni VA, Ryley DA, Urato AC. The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond. Hum Reprod 2013; 28:160-171.
Salisbury AL, Ponder KL, Padbury JF, Lester BM. Fetal effects of psychoactive drugs. Clin Perinatol 2009; 36:595-619.
De Matteo R, Blasch N, Stokes V, Davis P, Harding R. Induced preterm birth in sheep: a suitable model for studying the developmental effects of moderately preterm birth. Reprod Sci 2010; 17:724-733.
Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2021; 78:481-489.
Muttoni S, Ardissino M, John C. Classical psychedelics for the treatment of depression and anxiety: A systematic review. J Affect Disord 2019; 258:11-24.
Zeifman RJ, Wagner AC, Monson CM, Carhart-Harris RL. How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change. J Affect Disord 2023; 334:100-112.
Knudsen GM. Sustained effects of single doses of classical psychedelics in humans. Neuropsychopharmacology 2023; 48:145-150.
Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA, Jr., Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev 2018; 70:621-660.
Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, Roggero P, Prefumo F, do Vale MS, Cardona-Perez JA, Maiz N, Cetin I, et al. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr 2021.
Tyls F, Palenicek T, Horacek J. Psilocybin--summary of knowledge and new perspectives. Eur Neuropsychopharmacol 2014; 24:342-356.
Dolder PC, Schmid Y, Steuer AE, Kraemer T, Rentsch KM, Hammann F, Liechti ME. Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects. Clin Pharmacokinet 2017; 56:1219-1230.
Fallon JK, Kicman AT, Henry JA, Milligan PJ, Cowan DA, Hutt AJ. Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans. Clin Chem 1999; 45:1058-1069.
Long SY. Does LSD induce chromosomal damage and malformations? A review of the literature. Teratology 1972; 6:75-90.