the use of different types of drugs, which are most commonly prescribed off‐label [34]. In addition to medications used for controlled ovarian stimulation, ovulation induction and the prevention of premature luteinization, women undergoing ART are sometimes prescribed treatment “add‐ons” whose efficacy remains unproven. Furthermore, there is a lack of data on the safety of add‐on treatments, and there is the potential for interactions with other drugs [35]. It is thus unsurprising that many of the drugs routinely used in ART are contraindicated once a woman conceives, due to suspected or proven effects on fetal development (Table 7.3) [19,21,34,36–38].
Herbal medications in patients undergoing ART
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
|
