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{{short description|Medical treatment for low fertility}}
{{Multiple issues|
{{expert needed|date=February 2009}}
{{more medical citations needed|date=August 2020}}
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{{primary sources|date=August 2020}}
{{underlinked}}
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'''Fertility medications''', also known as '''fertility drugs''', are medications which enhance reproductive [[fertility]]. For women, fertility medication is used to stimulate [[ovarian follicle|follicle]] development of the [[ovary]].<ref>{{Cite book|last=Crowley|first=K|title=UpToDate|last2=Martin|first2=KA|last5=|publisher=UpToDate|year=2020|isbn=|editor-last=Post|editor-first=TW|location=|publication-place=Waltham, MA|publication-date=2020|pages=|chapter=Patient Education: Infertility in Women}}</ref> There are very few fertility medication options available for men.<ref>{{cite book |last1=Drobnis |first1=Erma Z |last2=Nangia |first2=Ajay K | name-list-format = vanc |title=Impacts of Medications on Male Fertility |date=2017 |publisher=Palgrave Macmillan |location=Cham, Switzerland |isbn=978-3-319-69535-8 |url=https://www.springer.com/gp/book/9783319695341 |access-date=23 February 2019}}</ref>
'''Fertility medications''', also known as '''fertility drugs''', are medications which enhance reproductive [[fertility]]. For women, fertility medication is used to stimulate [[ovarian follicle|follicle]] development of the [[ovary]].<ref>{{Cite book| vauthors = Crowley F, Martin KA |title=UpToDate |publisher=UpToDate|year=2020 | veditors = Post TW | location = Waltham, MA |chapter=Patient Education: Infertility in Women }}</ref> There are very few fertility medication options available for men.<ref>{{cite book | vauthors = Drobnis EZ, Nangia AK |title=Impacts of Medications on Male Fertility |date=2017 |publisher=Palgrave Macmillan |location=Cham, Switzerland |isbn=978-3-319-69535-8 |url=https://www.springer.com/gp/book/9783319695341 |access-date=23 February 2019}}</ref>


Agents that enhance ovarian activity can be classified as either [[gonadotropin releasing hormone]], [[estrogen]] [[Receptor antagonist|antagonists]] or [[gonadotropins]]. Treatment decision-making involves four major factors: efficacy, burden of treatment (such as frequency of injections and office visits), safety, and financial costs.<ref>{{cite journal | vauthors = Dancet EA, Fleur Dancet EA, D'Hooghe TM, d'Hooghe TM, van der Veen F, Bossuyt P, Sermeus W, Mol BW, Repping S | display-authors = 6 | title = "Patient-centered fertility treatment": what is required? | journal = Fertility and Sterility | volume = 101 | issue = 4 | pages = 924–6 | date = April 2014 | pmid = 24502889 | doi = 10.1016/j.fertnstert.2013.12.045 }}</ref>
Agents that enhance ovarian activity can be classified as either [[gonadotropin releasing hormone]], [[estrogen]] [[Receptor antagonist|antagonists]] or [[gonadotropins]].{{medcn|date=August 2020}}
Treatment decision-making involves four major factors: efficacy, burden of treatment (such as frequency of injections and office visits), safety, and financial costs.<ref>{{cite journal | vauthors = Dancet EA, Fleur Dancet EA, D'Hooghe TM, d'Hooghe TM, van der Veen F, Bossuyt P, Sermeus W, Mol BW, Repping S | display-authors = 6 | title = "Patient-centered fertility treatment": what is required? | journal = Fertility and Sterility | volume = 101 | issue = 4 | pages = 924–6 | date = April 2014 | pmid = 24502889 | doi = 10.1016/j.fertnstert.2013.12.045 | doi-access = free }}</ref>


==Female==
==Female==
===Main techniques===
===Main techniques===
The main techniques involving fertility medication in females are:
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]]
*[[Ovulation induction]], with the aim of producing one or two ovulatory follicles for [[Human fertilization|fertilization]] by [[sexual intercourse]] or [[artificial insemination]]
*[[Controlled ovarian hyperstimulation]], which is generally part of [[in vitro fertilization]], and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8&nbsp;mm in diameter),<ref name=chicago>[http://www.advancedfertility.com/antralfollicles.htm Antral Follicle Counts, Resting Follicles, Ovarian Volume and Ovarian Reserve. Testing of egg supply and predicting response to ovarian stimulation drugs] Advanced Fertility Center of Chicago. Retrieved on October 2, 2009</ref> followed by [[transvaginal oocyte retrieval]], co-incubation, followed by [[embryo transfer]] of a maximum of two embryos at a time.<ref name=nice2013>{{cite web | title = Fertility problems: assessment and treatment | url = http://guidance.nice.org.uk/CG156 | work = [[NICE guidelines|NICE clinical guideline]] CG156 | publisher = U.K. National Institute for Health and Care Excellence (NICE) | date = February 2013 }}</ref>
*[[Controlled ovarian hyperstimulation]], which is generally part of [[in vitro fertilization]], and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8&nbsp;mm in diameter),{{medcn|date=August 2020}} followed by [[transvaginal oocyte retrieval]], co-incubation, followed by [[embryo transfer]] of a maximum of two embryos at a time.<ref name=nice2013>{{cite web | title = Fertility problems: assessment and treatment | url = http://guidance.nice.org.uk/CG156 | work = [[NICE guidelines|NICE clinical guideline]] CG156 | publisher = U.K. National Institute for Health and Care Excellence (NICE) | date = February 2013 }}</ref>
*[[Final maturation induction]] of follicles, also triggering a predictable time of ovulation.
*[[Final maturation induction]] of follicles, also triggering a predictable time of ovulation.

=== Classification ===
The treatment of ovulatory dysfunction is based on the underlying cause of [[anovulation]], which is categorized into three different groups per [[World Health Organization|WHO]] guidelines.<ref>{{cite web|title=Classification of ovulatory disorders | work = eLearning | publisher = Royal College of Obstetricians and Gynaecologists |url=https://elearning.rcog.org.uk//ovulatory-dysfunction/classification-ovulatory-disorders|access-date=2020-07-28 }}</ref> Most fertility treatment approaches target class 2 patients.
{| class="wikitable"
|+Anovulation classes per World Health Organization
!WHO Class (percent prevalence)
!Type of anovulation
|-
|Class 1: Hypogonadotropic hypogonadal anovulation (hypothalamic amenorrhea) (10%)
|Low serum follicle stimulating hormone ([[Follicle-stimulating hormone|FSH]]) concentrations and low serum [[estradiol]] concentrations from decreased hypothalamic secretion of gonadotropic-releasing hormone ([[Gonadotropin-releasing hormone|GnRH]]) or lack of pituitary response.
|-
|Class 2: Normogonadotropic normoestrogenic anovulation (85%)
|FSH secretion during the follicular phase of the ovulation cycle is abnormal. This is commonly seen in women with polycystic ovary syndrome ([[Polycystic ovary syndrome|PCOS]]).
|-
|Class 3: Hypergonadotropic hypoestrogenic anovulation (5%)
|Premature ovarian failure due to early menopause and/or ovarian resistance.
|}


===Gonadotropin-releasing hormone===
===Gonadotropin-releasing hormone===
{{Main|Gonadotropin-releasing hormone}}
{{Main|Gonadotropin-releasing hormone}}


Either [[gonadotropin-releasing hormone]] (GnRH) or any [[gonadotropin-releasing hormone agonist]] (such as [[Lupron]]) may be used in combination with [[luteinizing hormone]] (LH) using an infusion pump to simulate endogenous hormone production. GnRH stimulates the release of gonadotropins (LH and FSH) from the anterior pituitary in the body. This set of therapy is reserved for class 1 patients and have produced ovulation rates of 90% and pregnancy rates of 80% or higher.{{medcn}}
Either [[gonadotropin-releasing hormone]] (GnRH) or any [[gonadotropin-releasing hormone agonist]] (such as [[Lupron]]) may be used in combination with [[luteinizing hormone]] (LH) using an infusion pump to simulate endogenous hormone production. [[Gonadotropin-releasing hormone|GnRH]] stimulates the release of gonadotropins (LH and FSH) from the anterior pituitary in the body. This set of therapy is reserved for a subset of women with infertility and have produced ovulation rates of 90% and pregnancy rates of 80% or higher.{{medcn|date=August 2020}}


===Antiestrogens===
===Antiestrogens===
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====Selective estrogen receptor modulators====
====Selective estrogen receptor modulators====
[[Clomiphene]] is a [[selective estrogen receptor modulator]] (SERM).<ref>{{cite journal |vauthors=Stute P, Birkhauser M |s2cid=23400904 |title=Selective estrogen receptor modulators (SERM)/Selektive Ostrogenrezeptormodulatoren (SERM). |journal=Gynakologische Endokrinologie |date=2015 |volume=13 |issue=2 |page=126 |doi=10.1007/s10304-015-0003-9 }}</ref> It is the most widely used fertility drug.<ref>{{cite journal | vauthors = Fauser BC | s2cid = 8380091 | title = Reproductive endocrinology: revisiting ovulation induction in PCOS | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 12 | pages = 704–5 | date = December 2014 | pmid = 25178733 | doi = 10.1038/nrendo.2014.156 }}</ref> Other medications in this class include [[tamoxifen]] and [[raloxifene]], although both are not as effective as clomiphene and are thus less widely used for fertility purposes.<ref>{{cite journal | vauthors = Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L | title = A pharmacological review of selective oestrogen receptor modulators | journal = Human Reproduction Update | volume = 6 | issue = 3 | pages = 212–24 | date = 2000 | pmid = 10874566 | doi = 10.1093/humupd/6.3.212 }}</ref> They are used in [[ovulation induction]] by inhibiting the negative feedback of estrogen at the hypothalamus. As the negative feedback of estrogen is inhibited, the hypothalamus secretes GnRh which in turn stimulates the anterior pituitary to secrete LH and FSH which help in ovulation. Between 60 and 85% of women, mostly with PCOS, ovulate successfully in response to clomiphene with a cumulative pregnancy rate of 30 to 40%.<ref>{{cite journal | vauthors = Dickey RP, Holtkamp DE | title = Development, pharmacology and clinical experience with clomiphene citrate | journal = Human Reproduction Update | volume = 2 | issue = 6 | pages = 483–506 | date = 1996 | pmid = 9111183 | doi = 10.1093/humupd/2.6.483 }}</ref><ref>{{cite journal | vauthors = Gorlitsky GA, Kase NG, Speroff L | title = Ovulation and pregnancy rates with clomiphene citrate | journal = Obstetrics and Gynecology | volume = 51 | issue = 3 | pages = 265–9 | date = March 1978 | pmid = 628527 | doi = 10.1097/00006250-197803000-00002 }}</ref><ref>{{cite journal | vauthors = Gysler M, March CM, Mishell DR, Bailey EJ | title = A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test | journal = Fertility and Sterility | volume = 37 | issue = 2 | pages = 161–7 | date = February 1982 | pmid = 7060766 | doi = 10.1016/s0015-0282(16)46033-4 }}</ref>
[[Clomiphene]] is a [[selective estrogen receptor modulator]] (SERM).<ref>{{cite journal |vauthors=Stute P, Birkhauser M |s2cid=23400904 |title=Selective estrogen receptor modulators (SERM)/Selektive Ostrogenrezeptormodulatoren (SERM). |journal=Gynakologische Endokrinologie |date=2015 |volume=13 |issue=2 |page=126 |doi=10.1007/s10304-015-0003-9 |url=http://doc.rero.ch/record/332590/files/10304_2015_Article_3.pdf }}</ref> It is the most widely used fertility drug.<ref>{{cite journal | vauthors = Fauser BC | title = Reproductive endocrinology: revisiting ovulation induction in PCOS | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 12 | pages = 704–5 | date = December 2014 | pmid = 25178733 | doi = 10.1038/nrendo.2014.156 | s2cid = 8380091 }}</ref> Other medications in this class include [[tamoxifen]] and [[raloxifene]], although both are not as effective as clomiphene and are thus less widely used for fertility purposes.<ref>{{cite journal | vauthors = Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L | title = A pharmacological review of selective oestrogen receptor modulators | journal = Human Reproduction Update | volume = 6 | issue = 3 | pages = 212–24 | date = 2000 | pmid = 10874566 | doi = 10.1093/humupd/6.3.212 | doi-access = free }}</ref> They are used in [[ovulation induction]] by inhibiting the negative feedback of estrogen at the hypothalamus. As the negative feedback of estrogen is inhibited, the hypothalamus secretes GnRh which in turn stimulates the anterior pituitary to secrete LH and FSH which help in ovulation. Between 60 and 85% of women, mostly with [[polycystic ovary syndrome]] (PCOS), ovulate successfully in response to clomiphene with a cumulative pregnancy rate of 30 to 40%.<ref>{{cite journal | vauthors = Dickey RP, Holtkamp DE | title = Development, pharmacology and clinical experience with clomiphene citrate | journal = Human Reproduction Update | volume = 2 | issue = 6 | pages = 483–506 | date = 1996 | pmid = 9111183 | doi = 10.1093/humupd/2.6.483 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gorlitsky GA, Kase NG, Speroff L | title = Ovulation and pregnancy rates with clomiphene citrate | journal = Obstetrics and Gynecology | volume = 51 | issue = 3 | pages = 265–9 | date = March 1978 | pmid = 628527 | doi = 10.1097/00006250-197803000-00002 }}</ref><ref>{{cite journal | vauthors = Gysler M, March CM, Mishell DR, Bailey EJ | title = A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test | journal = Fertility and Sterility | volume = 37 | issue = 2 | pages = 161–7 | date = February 1982 | pmid = 7060766 | doi = 10.1016/s0015-0282(16)46033-4 | doi-access = free }}</ref>


====Aromatase inhibitors ====
====Aromatase inhibitors ====
{{Main|Aromatase inhibitor}}
{{Main|Aromatase inhibitor}}
Although primarily a breast cancer treatment, [[aromatase inhibitor]]s (generic Letrozole) are also used in [[ovulation induction]]. Aromatase inhibitors are a common fertility treatment to treat women with PCOS. A meta-analysis analyzing live birth rates for women with PCOS treated with clomiphene compared to letrozole found that letrozole resulted in higher live birth rates.<ref>{{cite journal | vauthors = Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C | title = Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 5 | pages = CD010287 | date = May 2018 | pmid = 29797697 | pmc = 6494577 | doi = 10.1002/14651858.CD010287.pub3 }}</ref> However, ovulation induction remains an off-label indication which affects patient use.
Although primarily used in [[breast cancer treatment]], [[aromatase inhibitor]]s (particularly generic [[letrozole]]) are also used in [[ovulation induction]]. Aromatase inhibitors are a common fertility treatment to treat women with PCOS. A [[meta-analysis]] analyzing [[live birth rate]]s for women with PCOS treated with clomiphene compared to letrozole found that letrozole resulted in higher live birth rates.<ref>{{Cite journal |last1=Franik |first1=Sebastian |last2=Le |first2=Quang-Khoi |last3=Kremer |first3=Jan Am |last4=Kiesel |first4=Ludwig |last5=Farquhar |first5=Cindy |date=2022-09-27 |title=Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=9 |pages=CD010287 |doi=10.1002/14651858.CD010287.pub4 |issn=1469-493X |pmc=9514207 |pmid=36165742}}</ref> However, ovulation induction remains an [[off-label]] indication, which affects use.


===Gonadotropins===
===Gonadotropins===
{{Main|Gonadotropin preparations}}
{{Main|Gonadotropin preparations}}
[[Gonadotropins]] are protein hormones that stimulate the [[gonads]] (testes and ovaries). For medication, they can be extracted from urine in [[Menopause|postmenopausal women]] or through genetic modification and [[bacterial recombination]]. Examples of recombinant FSH are [[Follistim]] and Gonal F, while Luveris is a recombinant LH. FSH and recombinant FSH analogues are mainly used for [[controlled ovarian hyperstimulation]] as well as [[ovulation induction]].<ref>{{cite journal | vauthors = Conforti A, Esteves SC, Di Rella F, Strina I, De Rosa P, Fiorenza A, Zullo F, De Placido G, Alviggi C | display-authors = 6 | title = The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis | journal = Reproductive Biology and Endocrinology | volume = 17 | issue = 1 | pages = 18 | date = February 2019 | pmid = 30728019 | pmc = 6366097 | doi = 10.1186/s12958-019-0460-4 }}</ref> There has been some controversy over the efficacy between extracted and recombinant FSH for ovulation induction; however, a meta-analysis of 14 trials among 1726 women found that there were no differences in clinical pregnancy or live birth outcomes.<ref>{{cite journal | vauthors = Weiss NS, Kostova E, Nahuis M, Mol BW, van der Veen F, van Wely M | title = Gonadotrophins for ovulation induction in women with polycystic ovary syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD010290 | date = January 2019 | pmid = 30648738 | pmc = 6353048 | doi = 10.1002/14651858.CD010290.pub3 }}</ref>
[[Gonadotropins]] are protein hormones that stimulate the [[gonads]] (testes and ovaries). For medication, they can be extracted from urine in [[Menopause|postmenopausal women]] or through genetic modification and [[bacterial recombination]]. Examples of recombinant FSH are [[Follistim]] and Gonal F, while Luveris is a recombinant LH. FSH and recombinant FSH analogues are mainly used for [[controlled ovarian hyperstimulation]] as well as [[ovulation induction]].<ref>{{cite journal | vauthors = Conforti A, Esteves SC, Di Rella F, Strina I, De Rosa P, Fiorenza A, Zullo F, De Placido G, Alviggi C | display-authors = 6 | title = The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis | journal = Reproductive Biology and Endocrinology | volume = 17 | issue = 1 | pages = 18 | date = February 2019 | pmid = 30728019 | pmc = 6366097 | doi = 10.1186/s12958-019-0460-4 | doi-access = free }}</ref> There has been some controversy over the efficacy between extracted and recombinant FSH for ovulation induction; however, a meta-analysis of 14 trials among 1726 women found that there were no differences in clinical pregnancy or live birth outcomes.<ref>{{cite journal | vauthors = Weiss NS, Kostova E, Nahuis M, Mol BW, van der Veen F, van Wely M | title = Gonadotrophins for ovulation induction in women with polycystic ovary syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD010290 | date = January 2019 | issue = 1 | pmid = 30648738 | pmc = 6353048 | doi = 10.1002/14651858.CD010290.pub3 }}</ref>


Chemotherapy treatment in premenopausal women can compromise ovarian reserve and function, with gonadotoxic effects ranging from temporary to permanent infertility and [[Premature ovarian failure|premature ovarian failure (POF)]]. Proposed mechanisms for chemotherapy-induced ovarian damage include [[apoptosis]] of growing follicles, [[fibrosis]] of stromal cells, and injury to blood vessels resulting in [[ischemia]]. First-line options for fertility preservation include embryo and oocyte preservation before starting chemotherapy, though these methods do not contribute to the preservation of gonadal function. [[Gonadotropin-releasing hormone agonist|GnRH agonist]] therapies have been associated with relatively low risk, time, and cost.<ref>{{cite journal | vauthors = Hickman LC, Llarena NC, Valentine LN, Liu X, Falcone T | title = Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists | journal = Journal of Assisted Reproduction and Genetics | volume = 35 | issue = 4 | pages = 571–581 | date = April 2018 | pmid = 29470701 | pmc = 5949114 | doi = 10.1007/s10815-018-1128-2 | url = https://doi.org/10.1007/s10815-018-1128-2 }}</ref> There is evidence that chemotherapy cotreatment with gonadotropin-releasing hormone (GnRH) can increase the probability of spontaneous menses and ovulation resumption. However, this cotreatment has not shown an improvement in pregnancy rates.<ref>{{cite journal | vauthors = Bedaiwy MA, Abou-Setta AM, Desai N, Hurd W, Starks D, El-Nashar SA, Al-Inany HG, Falcone T | display-authors = 6 | title = Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis | journal = Fertility and Sterility | volume = 95 | issue = 3 | pages = 906–14.e1-4 | date = March 2011 | pmid = 21145541 | doi = 10.1016/j.fertnstert.2010.11.017 }}</ref>
Chemotherapy treatment in premenopausal women can compromise ovarian reserve and function, with gonadotoxic effects ranging from temporary to permanent infertility and [[Premature ovarian failure|premature ovarian failure (POF)]]. Proposed mechanisms for chemotherapy-induced ovarian damage include [[apoptosis]] of growing follicles, [[fibrosis]] of stromal cells, and injury to [[Blood vessel|blood vessels]] resulting in [[ischemia]]. First-line options for fertility preservation include embryo and oocyte preservation before starting chemotherapy, though these methods do not contribute to the preservation of gonadal function. [[Gonadotropin-releasing hormone agonist|GnRH agonist]] therapies have been associated with relatively low risk, time, and cost.<ref>{{cite journal | vauthors = Hickman LC, Llarena NC, Valentine LN, Liu X, Falcone T | title = Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists | journal = Journal of Assisted Reproduction and Genetics | volume = 35 | issue = 4 | pages = 571–581 | date = April 2018 | pmid = 29470701 | pmc = 5949114 | doi = 10.1007/s10815-018-1128-2 }}</ref> There is evidence that chemotherapy cotreatment with gonadotropin-releasing hormone (GnRH) can increase the probability of spontaneous menses and ovulation resumption. However, this cotreatment has not shown an improvement in pregnancy rates.<ref>{{cite journal | vauthors = Bedaiwy MA, Abou-Setta AM, Desai N, Hurd W, Starks D, El-Nashar SA, Al-Inany HG, Falcone T | display-authors = 6 | title = Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis | journal = Fertility and Sterility | volume = 95 | issue = 3 | pages = 906–14.e1–4 | date = March 2011 | pmid = 21145541 | doi = 10.1016/j.fertnstert.2010.11.017 | doi-access = free }}</ref>


===Human chorionic gonadotropin===
===Human chorionic gonadotropin===
{{Main|Human chorionic gonadotropin#Use as medication}}
{{Main|Human chorionic gonadotropin#Use as medication}}
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.<ref name="pmid24714837">{{cite journal | vauthors = Leão R, Esteves SC | title = Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech | journal = Clinics | volume = 69 | issue = 4 | pages = 279–93 | date = 2014 | pmid = 24714837 | pmc = 3971356 | doi = 10.6061/clinics/2014(04)10 |type= Review}}</ref> It is crucial in maintaining pregnancy, from the stages of placentation through to early embryo development.<ref name="pmid24714837"/> It is also used in assisted reproductive techniques as it can be used to replace LH in [[final maturation induction]].<ref name="pmid24714837"/>
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.<ref name="pmid24714837">{{cite journal | vauthors = Leão R, Esteves SC | title = Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech | journal = Clinics | volume = 69 | issue = 4 | pages = 279–93 | date = 2014 | pmid = 24714837 | pmc = 3971356 | doi = 10.6061/clinics/2014(04)10 | type = Review }}</ref> It is crucial in maintaining pregnancy, from the stages of placentation to early embryo development.<ref name="pmid24714837"/> It is also used in assisted reproductive techniques as it can be used to replace LH in [[final maturation induction]].<ref name="pmid24714837"/>


=== Other Medications ===
=== Other medications ===
⚫
Although [[metformin]] has been used off-label to treat [[oligomenorrhea]] and [[Ovarian hyperstimulation syndrome|ovarian hyperstimulation syndrome (OHSS)]] in women with PCOS, metformin is no longer recommended as infertility treatment per the [[American Society for Reproductive Medicine|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.<ref>{{cite journal | vauthors = Penzias A, Bendikson K, Butts S, Coutifaris C, Falcone T, Fossum G, Gitlin S, Gracia C, Hansen K, La Barbera A, Mersereau J | display-authors = 6 | title = Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline | journal = Fertility and Sterility | volume = 108 | issue = 3 | pages = 426–441 | date = September 2017 | pmid = 28865539 | doi = 10.1016/j.fertnstert.2017.06.026 | doi-access = free }}</ref>
{{unreferenced section|date=August 2020}}
⚫
Although [[metformin]] has been used off-label to treat [[oligomenorrhea]] and [[Ovarian hyperstimulation syndrome|ovarian hyperstimulation syndrome (OHSS)]] in women with [[Polycystic ovary syndrome|Polycystic Ovary Syndrome (PCOS)]], metformin is no longer recommended as infertility treatment per the [[American Society for Reproductive Medicine|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 patients 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.


==Male==
==Male==
Testosterone therapy (TTh), which aims to restore testosterone levels to mid-normal ranges in men diagnosed with late-onset hypogonadism (LOH), is an approved treatment.<ref>{{cite journal |vauthors=Rastrelli G, Maggi M, Corona G |title=Pharmacological management of late-onset hypogonadism |journal=Expert Rev Clin Pharmacol |volume=11 |issue=4 |pages=439–458 |date=April 2018 |pmid=29505313 |doi=10.1080/17512433.2018.1445969 |type= Review}}</ref>
Treatment for [[oligospermia]] is centered around underlying causes, such as endocrine and systematic disorders that can cause hypogonadism.<ref>{{cite journal | vauthors = de Kretser DM | title = Male infertility | journal = Lancet | volume = 349 | issue = 9054 | pages = 787–90 | date = March 1997 | pmid = 9074589 | doi = 10.1016/s0140-6736(96)08341-9 | s2cid = 12928678 | type = Review }}</ref>


Treatment for [[oligospermia]] is centered around underlying causes, such as endocrine and systematic disorders that can cause hypogonadism.<ref>{{cite journal | vauthors = de Kretser DM | title = Male infertility | journal = Lancet | volume = 349 | issue = 9054 | pages = 787–90 | date = March 1997 | pmid = 9074589 | doi = 10.1016/s0140-6736(96)08341-9 |type= Review}}</ref>
Typically, other [[Assisted reproductive technology|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.<ref>{{cite journal | vauthors = Ribeiro MA, Gameiro LF, Scarano WR, Briton-Jones C, Kapoor A, Rosa MB, El Dib R | title = Aromatase inhibitors in the treatment of oligozoospermic or azoospermic men: a systematic review of randomized controlled trials | journal = JBRA Assisted Reproduction | volume = 20 | issue = 2 | pages = 82–8 | date = May 2016 | pmid = 27244767 | doi = 10.5935/1518-0557.20160019 | type = Review | doi-access = free }}</ref>


Typically, other [[Assisted reproductive technology|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.<ref>{{cite journal | vauthors = Ribeiro MA, Gameiro LF, Scarano WR, Briton-Jones C, Kapoor A, Rosa MB, El Dib R | title = Aromatase inhibitors in the treatment of oligozoospermic or azoospermic men: a systematic review of randomized controlled trials | journal = Assisted Reproduction | volume = 20 | issue = 2 | pages = 82–8 | date = May 2016 | pmid = 27244767 | doi = 10.5935/1518-0557.20160019 |type= Review}}</ref>
Though there is no FDA indication for the use of [[clomiphene]] in male infertility, it has been prescribed since the 1960s.<ref name=Willets2013/> As of 2013, there is not substantial evidence to suggest that clomiphene can treat male infertility.<ref name= Willets2013>{{cite journal | vauthors = Willets AE, Corbo JM, Brown JN | title = Clomiphene for the treatment of male infertility | journal = Reproductive Sciences | volume = 20 | issue = 7 | pages = 739–44 | date = July 2013 | pmid = 23202725 | doi = 10.1177/1933719112466304 | type = Review | s2cid = 206804686 }}</ref>


⚫
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.<ref>{{cite journal | vauthors = Buhling K, Schumacher A, Eulenburg CZ, Laakmann E | title = Influence of oral vitamin and mineral supplementation on male infertility: a meta-analysis and systematic review | journal = Reproductive Biomedicine Online | volume = 39 | issue = 2 | pages = 269–279 | date = August 2019 | pmid = 31160241 | doi = 10.1016/j.rbmo.2019.03.099 | doi-access = free }}</ref> Folate in combination with zinc supplementation was shown to have a statistically significant effect on sperm concentration and morphology when compared to placebo.<ref>{{cite journal | vauthors = Irani M, Amirian M, Sadeghi R, Lez JL, Latifnejad Roudsari R | title = The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis | journal = Urology Journal | volume = 14 | issue = 5 | pages = 4069–4078 | date = August 2017 | pmid = 28853101 }}</ref> 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.<ref>{{cite journal | vauthors = Arab A, Hadi A, Moosavian SP, Askari G, Nasirian M | title = The association between serum vitamin D, fertility and semen quality: A systematic review and meta-analysis | journal = International Journal of Surgery | volume = 71 | pages = 101–109 | date = November 2019 | pmid = 31561004 | doi = 10.1016/j.ijsu.2019.09.025 | s2cid = 203580672 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Smits RM, Mackenzie-Proctor R, Fleischer K, Showell MG | title = Antioxidants in fertility: impact on male and female reproductive outcomes | journal = Fertility and Sterility | volume = 110 | issue = 4 | pages = 578–580 | date = September 2018 | pmid = 30196940 | doi = 10.1016/j.fertnstert.2018.05.028 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Chehab M, Madala A, Trussell JC | title = On-label and off-label drugs used in the treatment of male infertility | journal = Fertility and Sterility | volume = 103 | issue = 3 | pages = 595–604 | date = March 2015 | pmid = 25660648 | doi = 10.1016/j.fertnstert.2014.12.122 | type = Review | doi-access = free }}</ref>
Though there is no FDA indication for the use of [[clomiphene]] in male infertility, it has been prescribed since the 1960s.<ref name=Willets2013/> As of 2013, there is not substantial evidence to suggest that clomiphene can treat male infertility.<ref name= Willets2013>{{cite journal | vauthors = Willets AE, Corbo JM, Brown JN | title = Clomiphene for the treatment of male infertility | journal = Reproductive Sciences | volume = 20 | issue = 7 | pages = 739–44 | date = July 2013 | pmid = 23202725 | doi = 10.1177/1933719112466304 | s2cid = 206804686 |type= Review}}</ref>


⚫
As of September 2017, [[mesenchymal stem cell]] therapy for infertility has been studied in animals, but has not entered clinical trials.<ref name= Fazeli2018>{{cite journal | vauthors = Fazeli Z, Abedindo A, Omrani MD, Ghaderian SM | s2cid = 44236281 | title = Mesenchymal Stem Cells (MSCs) Therapy for Recovery of Fertility: a Systematic Review | journal = Stem Cell Reviews and Reports | volume = 14 | issue = 1 | pages = 1–12 | date = February 2018 | pmid = 28884412 | doi = 10.1007/s12015-017-9765-x }}</ref> 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.<ref name= Fazeli2018/>
⚫
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.<ref>{{cite journal | vauthors = Buhling K, Schumacher A, Eulenburg CZ, Laakmann E | title = Influence of oral vitamin and mineral supplementation on male infertility: a meta-analysis and systematic review | journal = Reproductive Biomedicine Online | volume = 39 | issue = 2 | pages = 269–279 | date = August 2019 | pmid = 31160241 | doi = 10.1016/j.rbmo.2019.03.099 }}</ref> Folate in combination with zinc supplementation was shown to have a statistically significant effect on sperm concentration and morphology when compared to placebo.<ref>{{cite journal | vauthors = Irani M, Amirian M, Sadeghi R, Lez JL, Latifnejad Roudsari R | title = The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis | journal = Urology Journal | volume = 14 | issue = 5 | pages = 4069–4078 | date = August 2017 | pmid = 28853101 }}</ref> 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.<ref>{{cite journal | vauthors = Arab A, Hadi A, Moosavian SP, Askari G, Nasirian M | title = The association between serum vitamin D, fertility and semen quality: A systematic review and meta-analysis | journal = International Journal of Surgery | volume = 71 | pages = 101–109 | date = November 2019 | pmid = 31561004 | doi = 10.1016/j.ijsu.2019.09.025 }}</ref> 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.<ref>{{cite journal|vauthors=Smits RM, Mackenzie-Proctor R, Fleischer K, Showell MG |title=Antioxidants in fertility: impact on male and female reproductive outcomes |journal=Fertil. Steril. |volume=110 |issue=4 |pages=578–580 |date=September 2018 |pmid=30196940 |doi=10.1016/j.fertnstert.2018.05.028 |url=}}</ref><ref>{{cite journal |vauthors=Chehab M, Madala A, Trussell JC |title=On-label and off-label drugs used in the treatment of male infertility |journal=Fertil. Steril. |volume=103 |issue=3 |pages=595–604 |date=March 2015 |pmid=25660648 |doi=10.1016/j.fertnstert.2014.12.122 |type= Review}}</ref>

⚫
As of September 2017, [[mesenchymal stem cell]] therapy for infertility has been studied in animals, but has not entered clinical trials.<ref name= Fazeli2018>{{cite journal |vauthors=Fazeli Z, Abedindo A, Omrani MD, Ghaderian SM |title=Mesenchymal Stem Cells (MSCs) Therapy for Recovery of Fertility: a Systematic Review |journal=Stem Cell Rev Rep |volume=14 |issue=1 |pages=1–12 |date=February 2018 |pmid=28884412 |doi=10.1007/s12015-017-9765-x}}</ref> 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.<ref name= Fazeli2018/>


==Adverse effects==
==Adverse effects==
{{unreferenced section|date=August 2020}}
=== Cancer ===
=== 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.<ref name=":1">{{cite journal | vauthors = Rizzuto I, Behrens RF, Smith LA | title = Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD008215 | date = June 2019 | issue = 6 | pmid = 31207666 | pmc = 6579663 | doi = 10.1002/14651858.cd008215.pub3 }}</ref> {{As of|2019|post=,}} 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.<ref name=":1" /> Most studies conducted have shown that fertility drugs do not increase the risk of other gynecologic cancers ([[Cervical cancer|cervical]] and [[Endometrial cancer|endometrial]]) or other malignant cancers ([[Thyroid cancer|thyroid]], [[Colorectal cancer|colon]], [[melanoma]], [[Breast cancer|breast]]).<ref name=":0">{{cite journal | vauthors = Kroener L, Dumesic D, Al-Safi Z | title = Use of fertility medications and cancer risk: a review and update | journal = Current Opinion in Obstetrics & Gynecology | volume = 29 | issue = 4 | pages = 195–201 | date = August 2017 | pmid = 28538003 | pmc = 5551049 | doi = 10.1097/GCO.0000000000000370 }}</ref> The validity of these data may be affected by patient-reported biases, small subject numbers, and other [[confounding]] variables.<ref name=":0" />
The use of fertility drugs is highly correlated with other ovarian cancer risk factors which complicates the direct contribution of the fertility drugs to ovarian cancer.{{cn|date=August 2020}}


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.<ref name="Rudant2012">{{cite journal | vauthors = Rudant J, Amigou A, Orsi L, Althaus T, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel G, Sirvent N, Chastagner P, Ducassou S, Rialland X, Hémon D, Clavel J | display-authors = 6 | title = Fertility treatments, congenital malformations, fetal loss, and childhood acute leukemia: the ESCALE study (SFCE) | journal = Pediatric Blood & Cancer | volume = 60 | issue = 2 | pages = 301–308 | date = February 2013 | pmid = 22610722 | doi = 10.1002/pbc.24192 | s2cid = 26010916 }}</ref>
Numerous studies indicate the risk of developing ovarian cancer as a result of fertility drugs is insignificant, but long-term exposure to fertility drugs may require further studies to determine their role in ovarian tumors and other health risks. Most studies conducted thus far have shown that fertility drugs also do not increase the risk of other gynecologic cancers ([[Cervical cancer|cervical]] and [[Endometrial cancer|endometrial]]) or other malignant cancers ([[Thyroid cancer|thyroid]], [[Colorectal cancer|colon]], [[melanoma]], [[Breast cancer|breast]]). However, the validity of these data may be affected by patient-reported biases, small subject numbers, and other [[confounding]] variables.{{medcn|date=August 2020}}


=== Ovarian hyperstimulation syndrome ===
=== Ovarian hyperstimulation syndrome ===
⚫
{{unreferenced section|date=August 2020}}

Estrogen antagonists and gonadotropins may stimulate multiple follicles and other ovarian hormones leading to [[multiple birth]] and possible [[ovarian hyperstimulation syndrome]] (OHSS). 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.
Estrogen antagonists and gonadotropins may stimulate multiple follicles and other ovarian hormones leading to [[multiple birth]] and possible [[ovarian hyperstimulation syndrome]] (OHSS).<ref>{{cite journal |vauthors=Banker M, Garcia-Velasco JA |title=Revisiting ovarian hyper stimulation syndrome: Towards OHSS free clinic |journal=J Hum Reprod Sci |volume=8 |issue=1 |pages=13–7 |date=2015 |pmid=25838743 |pmc=4381376 |doi=10.4103/0974-1208.153120 |doi-access=free }}</ref> 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 ==
== Discontinuation ==

Latest revision as of 01:55, 14 April 2024

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 gonadotropin releasing hormone, estrogen antagonists or gonadotropins.[medical citation needed]

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

[edit]

Main techniques

[edit]

The main techniques involving fertility medication in females are:

Gonadotropin-releasing hormone

[edit]
Main article: Gonadotropin-releasing hormone

Either gonadotropin-releasing hormone (GnRH) or any gonadotropin-releasing hormone agonist (such as Lupron) may be used in combination with luteinizing hormone (LH) using an infusion pump to simulate endogenous hormone production. GnRH stimulates the release of gonadotropins (LH and FSH) from the anterior pituitary in the body. This set of therapy is reserved for a subset of women with infertility and have produced ovulation rates of 90% and pregnancy rates of 80% or higher.[medical citation needed]

Antiestrogens

[edit]

Antiestrogens inhibit the effects of estrogen, which include selective estrogen receptor modulators (SERM) and aromatase inhibitors.

Hypothalamic–pituitary–gonadal axis in females, with estrogen exerting mainly negative feedback on FSH secretion from the pituitary gland.

Selective estrogen receptor modulators

[edit]

Clomiphene is a selective estrogen receptor modulator (SERM).[5] It is the most widely used fertility drug.[6] Other medications in this class include tamoxifen and raloxifene, although both are not as effective as clomiphene and are thus less widely used for fertility purposes.[7] They are used in ovulation induction by inhibiting the negative feedback of estrogen at the hypothalamus. As the negative feedback of estrogen is inhibited, the hypothalamus secretes GnRh which in turn stimulates the anterior pituitary to secrete LH and FSH which help in ovulation. Between 60 and 85% of women, mostly with polycystic ovary syndrome (PCOS), ovulate successfully in response to clomiphene with a cumulative pregnancy rate of 30 to 40%.[8][9][10]

Aromatase inhibitors

[edit]
Main article: Aromatase inhibitor

Although primarily used in breast cancer treatment, aromatase inhibitors (particularly generic letrozole) are also used in ovulation induction. Aromatase inhibitors are a common fertility treatment to treat women with PCOS. A meta-analysis analyzing live birth rates for women with PCOS treated with clomiphene compared to letrozole found that letrozole resulted in higher live birth rates.[11] However, ovulation induction remains an off-label indication, which affects use.

Gonadotropins

[edit]
Main article: Gonadotropin preparations

Gonadotropins are protein hormones that stimulate the gonads (testes and ovaries). For medication, they can be extracted from urine in postmenopausal women or through genetic modification and bacterial recombination. Examples of recombinant FSH are Follistim and Gonal F, while Luveris is a recombinant LH. FSH and recombinant FSH analogues are mainly used for controlled ovarian hyperstimulation as well as ovulation induction.[12] There has been some controversy over the efficacy between extracted and recombinant FSH for ovulation induction; however, a meta-analysis of 14 trials among 1726 women found that there were no differences in clinical pregnancy or live birth outcomes.[13]

Chemotherapy treatment in premenopausal women can compromise ovarian reserve and function, with gonadotoxic effects ranging from temporary to permanent infertility and premature ovarian failure (POF). Proposed mechanisms for chemotherapy-induced ovarian damage include apoptosis of growing follicles, fibrosis of stromal cells, and injury to blood vessels resulting in ischemia. First-line options for fertility preservation include embryo and oocyte preservation before starting chemotherapy, though these methods do not contribute to the preservation of gonadal function. GnRH agonist therapies have been associated with relatively low risk, time, and cost.[14] There is evidence that chemotherapy cotreatment with gonadotropin-releasing hormone (GnRH) can increase the probability of spontaneous menses and ovulation resumption. However, this cotreatment has not shown an improvement in pregnancy rates.[15]

Human chorionic gonadotropin

[edit]
Main article: Human chorionic gonadotropin § Use as medication

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

[edit]

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

[edit]

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 clomiphene in male infertility, it has been prescribed since the 1960s.[20] As of 2013, there is not substantial evidence to suggest that clomiphene can treat male infertility.[20]

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

[edit]

Cancer

[edit]

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, 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

[edit]

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

[edit]

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

[edit]

References

[edit]
  1. ^ Crowley F, Martin KA (2020). "Patient Education: Infertility in Women". In Post TW (ed.). UpToDate. Waltham, MA: UpToDate.
  2. ^ Drobnis EZ, Nangia AK (2017). Impacts of Medications on Male Fertility. Cham, Switzerland: Palgrave Macmillan. ISBN 978-3-319-69535-8. Retrieved 23 February 2019.
  3. ^ Dancet EA, Fleur Dancet EA, D'Hooghe TM, d'Hooghe TM, van der Veen F, Bossuyt P, et al. (April 2014). ""Patient-centered fertility treatment": what is required?". Fertility and Sterility. 101 (4): 924–6. doi:10.1016/j.fertnstert.2013.12.045. PMID 24502889.
  4. ^ "Fertility problems: assessment and treatment". NICE clinical guideline CG156. U.K. National Institute for Health and Care Excellence (NICE). February 2013.
  5. ^ Stute P, Birkhauser M (2015). "Selective estrogen receptor modulators (SERM)/Selektive Ostrogenrezeptormodulatoren (SERM)" (PDF). Gynakologische Endokrinologie. 13 (2): 126. doi:10.1007/s10304-015-0003-9. S2CID 23400904.
  6. ^ Fauser BC (December 2014). "Reproductive endocrinology: revisiting ovulation induction in PCOS". Nature Reviews. Endocrinology. 10 (12): 704–5. doi:10.1038/nrendo.2014.156. PMID 25178733. S2CID 8380091.
  7. ^ Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L (2000). "A pharmacological review of selective oestrogen receptor modulators". Human Reproduction Update. 6 (3): 212–24. doi:10.1093/humupd/6.3.212. PMID 10874566.
  8. ^ Dickey RP, Holtkamp DE (1996). "Development, pharmacology and clinical experience with clomiphene citrate". Human Reproduction Update. 2 (6): 483–506. doi:10.1093/humupd/2.6.483. PMID 9111183.
  9. ^ Gorlitsky GA, Kase NG, Speroff L (March 1978). "Ovulation and pregnancy rates with clomiphene citrate". Obstetrics and Gynecology. 51 (3): 265–9. doi:10.1097/00006250-197803000-00002. PMID 628527.
  10. ^ Gysler M, March CM, Mishell DR, Bailey EJ (February 1982). "A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test". Fertility and Sterility. 37 (2): 161–7. doi:10.1016/s0015-0282(16)46033-4. PMID 7060766.
  11. ^ Franik, Sebastian; Le, Quang-Khoi; Kremer, Jan Am; Kiesel, Ludwig; Farquhar, Cindy (2022-09-27). "Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome". The Cochrane Database of Systematic Reviews. 2022 (9): CD010287. doi:10.1002/14651858.CD010287.pub4. ISSN 1469-493X. PMC 9514207. PMID 36165742.
  12. ^ Conforti A, Esteves SC, Di Rella F, Strina I, De Rosa P, Fiorenza A, et al. (February 2019). "The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis". Reproductive Biology and Endocrinology. 17 (1): 18. doi:10.1186/s12958-019-0460-4. PMC 6366097. PMID 30728019.
  13. ^ Weiss NS, Kostova E, Nahuis M, Mol BW, van der Veen F, van Wely M (January 2019). "Gonadotrophins for ovulation induction in women with polycystic ovary syndrome". The Cochrane Database of Systematic Reviews. 1 (1): CD010290. doi:10.1002/14651858.CD010290.pub3. PMC 6353048. PMID 30648738.
  14. ^ Hickman LC, Llarena NC, Valentine LN, Liu X, Falcone T (April 2018). "Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists". Journal of Assisted Reproduction and Genetics. 35 (4): 571–581. doi:10.1007/s10815-018-1128-2. PMC 5949114. PMID 29470701.
  15. ^ Bedaiwy MA, Abou-Setta AM, Desai N, Hurd W, Starks D, El-Nashar SA, et al. (March 2011). "Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis". Fertility and Sterility. 95 (3): 906–14.e1–4. doi:10.1016/j.fertnstert.2010.11.017. PMID 21145541.
  16. ^ a b c Leão R, Esteves SC (2014). "Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech". Clinics (Review). 69 (4): 279–93. doi:10.6061/clinics/2014(04)10. PMC 3971356. PMID 24714837.
  17. ^ Penzias A, Bendikson K, Butts S, Coutifaris C, Falcone T, Fossum G, et al. (September 2017). "Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline". Fertility and Sterility. 108 (3): 426–441. doi:10.1016/j.fertnstert.2017.06.026. PMID 28865539.
  18. ^ de Kretser DM (March 1997). "Male infertility". Lancet (Review). 349 (9054): 787–90. doi:10.1016/s0140-6736(96)08341-9. PMID 9074589. S2CID 12928678.
  19. ^ Ribeiro MA, Gameiro LF, Scarano WR, Briton-Jones C, Kapoor A, Rosa MB, El Dib R (May 2016). "Aromatase inhibitors in the treatment of oligozoospermic or azoospermic men: a systematic review of randomized controlled trials". JBRA Assisted Reproduction (Review). 20 (2): 82–8. doi:10.5935/1518-0557.20160019. PMID 27244767.
  20. ^ a b Willets AE, Corbo JM, Brown JN (July 2013). "Clomiphene for the treatment of male infertility". Reproductive Sciences (Review). 20 (7): 739–44. doi:10.1177/1933719112466304. PMID 23202725. S2CID 206804686.
  21. ^ Buhling K, Schumacher A, Eulenburg CZ, Laakmann E (August 2019). "Influence of oral vitamin and mineral supplementation on male infertility: a meta-analysis and systematic review". Reproductive Biomedicine Online. 39 (2): 269–279. doi:10.1016/j.rbmo.2019.03.099. PMID 31160241.
  22. ^ Irani M, Amirian M, Sadeghi R, Lez JL, Latifnejad Roudsari R (August 2017). "The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis". Urology Journal. 14 (5): 4069–4078. PMID 28853101.
  23. ^ Arab A, Hadi A, Moosavian SP, Askari G, Nasirian M (November 2019). "The association between serum vitamin D, fertility and semen quality: A systematic review and meta-analysis". International Journal of Surgery. 71: 101–109. doi:10.1016/j.ijsu.2019.09.025. PMID 31561004. S2CID 203580672.
  24. ^ Smits RM, Mackenzie-Proctor R, Fleischer K, Showell MG (September 2018). "Antioxidants in fertility: impact on male and female reproductive outcomes". Fertility and Sterility. 110 (4): 578–580. doi:10.1016/j.fertnstert.2018.05.028. PMID 30196940.
  25. ^ Chehab M, Madala A, Trussell JC (March 2015). "On-label and off-label drugs used in the treatment of male infertility". Fertility and Sterility (Review). 103 (3): 595–604. doi:10.1016/j.fertnstert.2014.12.122. PMID 25660648.
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