Drug Use in IUI, IVF, ICSI:

How does each work?

Dr. Patsama Vichinsartvichai

OB-GYN and Reproductive Medicine Specialist

Minimally Invasive Surgery Specialist

MClinEmbryol, EFOG-EBCOG, EFRM-ESHRE/EBCOG.

Keywords: gonadotropin; IVF; ICSI; GnRH; LH; FSH; estradiol; progesterone; GnRH agonist; GnRH antagonist; dipherelin; triptorelin; ganirelix; cetrorelix; orgalutran; cetrotide; gonal-f; puregon; rekovelle; follitrope; menopur; ivf-m; ivf-c; ovidrel

Figure 1 The typical timeline for ovarian stimulation cycle

Patients undergoing infertility treatment, especially those who have experienced IVF procedures, often encounter a wide variety of medications, which can be confusing. The purpose of this article is to provide detailed information on these medications.

Ovarian Stimulation Phase

During the ovarian stimulation phase, various medications are used to stimulate the ovaries to produce multiple eggs. Here are the details:

Oral Stimulation Medications:

Clomiphene Citrate: This medication belongs to a group called Selective Estrogen Receptor Modulators (SERMs). It works by binding to estrogen receptors in various tissues, acting both as an estrogen receptor agonist and antagonist, depending on its molecular design. Clomiphene Citrate is commonly used in cases where the patient may need to stimulate ovulation and then attempt natural conception or intrauterine insemination (IUI). It can also be used for mild or minimal stimulation IVF protocols. This drug is typically taken in doses ranging from 1-3 tablets per day, starting on day 3 of the menstrual cycle for 5 days. The available clomiphene citrate is shown in Figure 2.

Figure 2 The variation of clomiphene citrate that available in Thailand.

Letrozole: This medication belongs to a group called aromatase inhibitors, which reduce estrogen levels and increase FSH production, stimulating follicle growth. Letrozole is used off-label for ovulation induction in cases similar to Clomiphene Citrate, including PCOS and mild IVF protocols. The typical dose is 2.5 mg per tablet, taken once daily for 5 days. The preparation of letrozole that available is presented in Figure 3.

Figure 3 The various preparations of letrozole that available in Thailand.

Injectable Stimulation Medications:

Gonal-F® (Follitropin Alfa): This is a recombinant FSH produced using Chinese hamster ovary cells. It is used to stimulate the growth of multiple follicles. Gonal-F is available in prefilled pens with dosages of 300, 450, and 900 IU (Figure 4). The dosage depends on the treatment protocol and individual response.

Figure 4 Various doses of Gonal-F prefilled pen available in the market (300, 450, and 900 IU).

Follitrope®: This is another form of recombinant FSH, similar to Gonal-F® (follitropin alpha). It comes in prefilled syringes with dosages of 75, 150, 225, and 300 IU as shown in Figure 5.

Figure 5 Various doses of Follitrope prefilled-syringe available in the market (75, 150, 225 and 300 IU).

Puregon® (Follitropin Beta): This is a recombinant FSH produced using Chinese hamster ovary cells. It comes in vials or prefilled cartridges. The dosage form includes 50 and 100 IU vials and 300 and 600 IU prefilled cartridges (Figure 6).

Figure 6 Various preparation and doses of Puregon in the market; 50 and 100 IU vials and 300 and 600 IU prefilled cartridge (must use with the Puregon Pen).

Rekovelle® (Follitropin Delta): This is a recombinant FSH produced using human fetal retinal cells. It comes in prefilled pens with dosages of 12, 36, and 72 mcg (Figure 7).

Figure 7 Various doses of Rekovelle prefilled-pen; 12, 36, and 72 mcg.

Menopur® (Human Menopausal Gonadotropin): This medication contains both FSH and LH, derived from the urine of postmenopausal women. It comes in vials of 75 IU and multidose vials of 600 IU and 1200 IU.

Figure 8 Various doses and preparations of Menopur; 75 IU vials, 600 and 1200 IU multidose.

IVF-M™ and IVF-M HP™: These are other forms of human menopausal gonadotropin without added hCG, available in 75 IU vials (Figure 9)

Figure 9 IVF-M and IVF-M HP 75 IU vials.

Elonva® (Corifollitropin Alfa): Elonva is a recombinant gonadrotopin where the tail-end of beta subunit of FSH hormone is tagged with the tail of hCG hormone instead. This make Elonva a long-acting gonadotropin reduces the frequency of injections (last for 7 days). It comes in prefilled syringes with dosages of 100 and 150 mcg (Figure 10).

Figure 10 100 and 150 mcg prefilled-syringe of Elonva.

Pergoveris®: This combination medication includes recombinant FSH (Follitropin Alfa) and recombinant LH (Lutropin Alfa), available in prefilled pens with dosages of 300, 450, and 900 IU.

Figure 10 100 and 150 mcg prefilled-syringe of Elonva.

Medications to Prevent Premature Ovulation

To prevent premature ovulation, medications ensure that the eggs are retrieved at the optimal time:

Figure 11 Medications that used to prevent premature LH surge; GnRH antagonist and progestogen.

GnRH Antagonists:

Orgalutran® (Ganirelix): A prefilled syringe used to inhibit premature LH surge, with a dosage of 250 mcg.

Cetrotide® (Cetrorelix): A vial that requires mixing before injection, with a dosage of 250 mcg.

Progestogens: Provera, Duphaston, Utrogestran: These medications suppress the LH surge by mimicking the effects of progesterone.

Triggering Ovulation

To trigger ovulation, medications ensure that the eggs are released for retrieval (Figure 12):

Figure 12 GnRH agonist, recombinant hCG and urinary hCG available for trigger of final oocyte maturation,

GnRH Agonists:

Decapeptyl® (Triptorelin): A prefilled syringe used as a trigger shot, with a dosage of 0.1 mg.

Diphereline® (Triptorelin): A vial that requires mixing before injection, with a dosage of 0.1 mg.

hCG Injections:

Ovidrel® (Choriogonadotropin Alpha): A recombinant hCG used in a prefilled pen, with a dosage of 250 mcg.

IVF-C: Derived from urine, available in vials for injection with a dosage of 5000 IU.

Preparing the Endometrial Lining for Embryo Transfer

The preparation of the endometrial lining involves the use of hormones to create an optimal environment for embryo implantation. A typical timeline for embryo transfer cycle is represented in Figure 13.

Fig 13 Timeline for embryo transfer cycle.

Figure 13 Timeline for embryo transfer cycle.

Estrogen:

Used in the first half of the menstrual cycle to thicken the endometrial lining. Available in oral and transdermal forms as seen in Figure 14.

Figure 14 Various forms of estrogen use in endometrium preparation.

Progesterone:

Used in the second half of the menstrual cycle to prepare the lining for implantation. Available in injectable and vaginal forms as shown in Figure 15.

Figure 15 Various preparation and route of progesterone using in endometrium preparation for embryo transfer.

Other Medications

Contraceptives: Used to regulate menstrual cycles or prepare the ovaries for treatment as in Figure 16.

Figure 16 Various preparation of oral contraceptive pills use in IVF treatment.

Miscellaneous Medications: For conditions like endometriosis, PCOS, or hyperprolactinemia, additional medications such as Metformin or Bromocriptine may be prescribed.