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The World Health Organization (WHO) estimates that in some parts of the world, up to 80% of the population regularly uses herbal medicines [39]. Couples undergoing ART are no exception and frequently resort to plant‐based products in hopes of maximizing treatment efficacy [40]. In an Irish study, 46% of ART patients reported using herbal medications regularly, with most ingesting such substances in the months immediately preceding treatment [41]. Commonly used herbal remedies in ART include echinacea, ginseng, “Chinese herbs,” “fertility herbs” with uncertain preparations, St. John’s wort, gingko biloba, valerian, agnus cactus, chasteberry, goji berry, mother wort and horse chestnut [41,42]. Despite their widespread use, herbal products are classified as dietary supplements and thus exempt from licensing requirements in countries such as the UK and USA [43], raising concerns about efficacy, variable composition and potential toxicity [44]. It is indeed unclear how these supplements affect the efficacy and safety of ART [42]. Furthermore, in patients undergoing oocyte retrieval or surgical sperm retrieval under anesthesia, the perioperative implications of herbal medicines must be considered. Some herbal medicines have been shown to increase the risk of bleeding, arrhythmias and hypoglycemia [43]. For this reason, the American Society of Anesthesiologists recommends discontinuing herbal medications 2–3 weeks prior to surgery [43,44].

Table 7.3 Approved and off‐label drugs used in ART [19,21,34,36–38].

Drug	Mechanism of action	Use in ART	FDA category / BNF advice	Known interactions
Aromatase inhibitors (e.g. letrozole, anastrazole)	Selective aromatase inhibitor	Off‐label: ovulation induction and mild COS in IVF	Category D BNF: contraindicated in pregnancy	Plasma concentrations reduced by concurrent administration of tamoxifen
Aspirin	COX inhibitor	Off‐label: unproven effect on implantation; treatment of APS	Low dose—not assigned Full dose—category D BNF: compatible (low dose); human data suggest risk in first and third trimesters (full dose)	Acetazolamide Anticoagulants Anticonvulsants Betablockers Diuretics Oral hypoglycemic agents
Clomiphene citrate	Selective estrogen receptor modulator	FDA: Ovulation induction Off‐label: mild COS in IVF	Category X BNF: contraindicated after conception has occurred	None known
Dexamethasone	Various	Off‐label: ovulation induction in clomid‐resistant PCOS; recurrent implantation failure	Category C BNF: increased risk of oral clefts	CYP3A inducers (e.g. carbamazepine, rifampicin) and inhibitors (e.g. clarithromycin)
Dehydroepiandrosterone (DHEA)	Testosterone precursor	Off‐label: prior to IVF in women with low ovarian reserve	FDA category not assigned BNF: animal data suggest risk, e.g. virilization of female fetuses	Bromocriptine Carbamazepine Dexamethasone Insulin Phenytoin
Dopamine agonists (e.g. Bromocriptine, Cabergoline)	D2 receptor agonists	FDA: hyperprolactinemic disorders Off‐label: infertility of pituitary origin; adjunct in the treatment of OHSS	Category B BNF: Bromocriptine: compatible with pregnancy Cabergoline: human data suggest low risk	Dopamine antagonists Antihypertensive drugs
Gonadotropins	Human gonadotropin analogues	FDA: ovarian stimulation and ovulation induction	Category X	None known
GnRH agonists	GnRH receptor agonists, desensitization with prolonged exposure	FDA: prevention of premature LH surge in women undergoing COS Off‐label: ovulation trigger in high responders	Category X	None known
GnRH antagonists	GnRH receptor blockers	FDA: prevention of premature LH surge in women undergoing COS Off‐label: treatment of OHSS	Category X	None known
hCG	LH analogue	FDA: ovulation induction in anovulatory women; follicular maturation in COS Off‐label: luteal phase support in IVF	Category X—intrauterine death	None known
hGH	IGF‐1 production	Off‐label: adjuvant therapy in low responders in IVF	Category B	None known
Intralipid infusions	Unclear—possible immune modulator	Off‐label: recurrent implantation failure / pregnancy loss	Category C BNF: compatible with pregnancy	Oxine
Intravenous immunoglobulin (IVIg)	Immune modulator	Off‐label: recurrent implantation failure / pregnancy loss	Category C BNF: compatible with pregnancy; no known embryo‐fetal risk	None known
Metformin	Various ‐ euglycemic	Off‐label: improvement of menstrual cycle regularity or hyperandrogenism in women with PCOS	Category B BNF: human data suggest low risk	Furosemide increases metformin concentration Nifedipine increases the absorption of metformin
Prednisolone	Various	Off‐label: treatment of APS	Category D BNF: increased risk of orofacial clefts	Anticoagulants CYP3A4 inducers and inhibitors NSAIDs
Progesterone	Sex steroid hormone	FDA: luteal phase support in ART	FDA category not assigned	None known
Sildenafil	Phosphodiesterase 5 inhibitor	Off‐label: female infertility with endometrial factor; increase endometrial thickness	Category B BNF: limited human data—animal data suggest low risk	Alpha blockers Anti‐hypertensives Nitrates CYP3A4 inhibitors (increase the concentration of sildenafil)
Tamoxifen	Selective estrogen receptor modulator	Off‐label: alternative to clomiphene in PCOS / women with thin endometrium in response to clomiphene	Category D BNF: contraindicated (fetal growth restriction, miscarriage and preterm birth)	Erythromycin Letrozole Nifedipine Rifampicin

ACE, angiotensin‐converting enzyme; APS, antiphospholipid syndrome; ART, assisted reproductive treatment; BNF, British National Formulary; COS, controlled ovarian stimulation; COX, cyclooxygenase; CYP, cytochrome P; FDA, Food and Drug Administration; GnRH, gonadotropin‐releasing hormone; hCG, human chorionic gonadotropin; hGH, human growth hormone; IGF, insulin‐like growth factor; IVF, in vitro; fertilization; LH, luteinizing hormone; NSAID, nonsteroidal anti‐inflammatory drug; OHSS, ovarian hyperstimulation syndrome; PCOS, polycystic ovary syndrome.