Fertility medication
This article needs more primary sources. (August 2020) |
Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary.[1] There are very few fertility medication options available for men.[2]
Agents that enhance ovarian activity can be classified as either
Treatment decision-making involves four major factors: efficacy, burden of treatment (such as frequency of injections and office visits), safety, and financial costs.[3]
Female
Main techniques
The main techniques involving fertility medication in females are:
- Ovulation induction, with the aim of producing one or two ovulatory follicles for fertilization by sexual intercourse or artificial insemination
- in vitro fertilization, and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8 mm in diameter),[medical citation needed] followed by transvaginal oocyte retrieval, co-incubation, followed by embryo transfer of a maximum of two embryos at a time.[4]
- Final maturation induction of follicles, also triggering a predictable time of ovulation.
Gonadotropin-releasing hormone
Either
Antiestrogens
Antiestrogens inhibit the effects of estrogen, which include selective estrogen receptor modulators (SERM) and aromatase inhibitors.
Selective estrogen receptor modulators
Aromatase inhibitors
Although primarily used in
Gonadotropins
Chemotherapy treatment in premenopausal women can compromise ovarian reserve and function, with gonadotoxic effects ranging from temporary to permanent infertility and
Human chorionic gonadotropin
Human chorionic gonadotropin (hCG), also known as the “hormone of pregnancy” is a hormone that is normally produced during pregnancy and plays an integral role throughout reproduction.[16] It is crucial in maintaining pregnancy, from the stages of placentation to early embryo development.[16] It is also used in assisted reproductive techniques as it can be used to replace LH in final maturation induction.[16]
Other medications
Although metformin has been used off-label to treat oligomenorrhea and ovarian hyperstimulation syndrome (OHSS) in women with PCOS, metformin is no longer recommended as infertility treatment per the American Society for Reproductive Medicine (ASRM) in 2017. Its use to treat anovulatory infertility was based on an association of insulin resistance in non-obese women with PCOS. While metformin may increase ovulation in women with PCOS, there is no evidence of increased pregnancy rates or live-birth rates, and the combination therapy of metformin and clomiphene citrate did not provide a significant benefit compared to clomiphene citrate alone. First-line therapy for ovulation induction in women with PCOS remains the anti-estrogen clomiphene citrate or the aromatase inhibitor letrozole.[17]
Male
Treatment for oligospermia is centered around underlying causes, such as endocrine and systematic disorders that can cause hypogonadism.[18]
Typically, other assisted reproductive technologies are used. Although there is no FDA indication for use of aromatase inhibitors improving spermatogenesis, testolactone has been shown to be effective when compared to placebo.[19]
Though there is no FDA indication for the use of
Combinations of vitamins and minerals, including selenium, co-enzyme Q10, L-carnitine, folic acid, zinc, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been shown to improve male infertility, but due to the low amounts of studies and participants, more clinical studies are needed.[21] Folate in combination with zinc supplementation was shown to have a statistically significant effect on sperm concentration and morphology when compared to placebo.[22] There is evidence suggesting a significant association between vitamin D serum concentrations and the quality of sperm in men, characterized by the sperm's motility and progress motility.[23] Because the quality of men's sperm is influenced by genetics, results should be interpreted cautiously. There is little evidence that supplementation with antioxidants, such as pentoxifylline will increase male fertility.[24][25]
As of September 2017, mesenchymal stem cell therapy for infertility has been studied in animals, but has not entered clinical trials.[26] Stem cells collected from bone marrow and umbilical cord have shown the most ability to rehabilitate fertility in animals, but more studies are needed to determine efficacy.[26]
Adverse effects
Cancer
Since infertility increases the risk of ovarian cancer, fertility drugs have been used to combat this but the cancer risks are still not completely known.[27] As of 2019,[update] there have been studies that have shown the risk of developing ovarian cancer is higher when taking fertility medications. However, due to the low number of studies, lack of follow-up time and other contribution factors, the risk is unclear.[27] Most studies conducted have shown that fertility drugs do not increase the risk of other gynecologic cancers (cervical and endometrial) or other malignant cancers (thyroid, colon, melanoma, breast).[28] The validity of these data may be affected by patient-reported biases, small subject numbers, and other confounding variables.[28]
Children born to mothers who use fertility medication to induce ovulation are more than twice as likely to develop leukemia during their childhoods than other children.[29]
Ovarian hyperstimulation syndrome
Estrogen antagonists and gonadotropins may stimulate multiple follicles and other ovarian hormones leading to multiple birth and possible ovarian hyperstimulation syndrome (OHSS).[30] Development of OHSS is dependent on the administration of hCG and is mediated through vascular endothelial growth factor (VEGF). OHSS is characterized as cystic enlargement of the ovaries. Multiple birth is especially deleterious due to compounding risks including premature delivery and low birthweight, pre-eclampisa, and increased risk of neonatal mortality. While triplet births have been declining in ART, multiple births remain over 50% of births from IVF. However, there are limitations to measure, as 4% to 8% IVF clinics to do not report their data to the CDC.
Discontinuation
Main reasons for discontinuation across all types of fertility treatment and treatment stage, are "postponement of treatment, physical and psychological burden and relational and personal problems".[31]
See also
References
- ^ Crowley F, Martin KA (2020). "Patient Education: Infertility in Women". In Post TW (ed.). UpToDate. Waltham, MA: UpToDate.
- ISBN 978-3-319-69535-8. Retrieved 23 February 2019.
- PMID 24502889.
- NICE clinical guidelineCG156. U.K. National Institute for Health and Care Excellence (NICE). February 2013.
- S2CID 23400904.
- S2CID 8380091.
- PMID 10874566.
- PMID 9111183.
- PMID 628527.
- PMID 7060766.
- PMID 36165742.
- PMID 30728019.
- PMID 30648738.
- PMID 29470701.
- PMID 21145541.
- ^ PMID 24714837.
- PMID 28865539.
- S2CID 12928678.
- PMID 27244767.
- ^ S2CID 206804686.
- PMID 31160241.
- PMID 28853101.
- S2CID 203580672.
- PMID 30196940.
- PMID 25660648.
- ^ S2CID 44236281.
- ^ PMID 31207666.
- ^ PMID 28538003.
- S2CID 26010916.
- PMID 25838743.
- PMID 22869759.