ART in Endometriosis

With both GnRH-a and GnRH antagonist protocols, controlled ovarian stimulation has similar IVF outcomes in patients with mild-to-moderate endometriosis.

However, agonist protocols have a significantly higher number of MII oocytes and available embryos that can be cryopreserved compared to patients treated with the antagonist protocol. The cumulative fecundity rate will be higher in the agonist protocol when the outcome of subsequent freeze-thaw cycles is considered.

1. Ultra Long Agonist protocol - GnRH Agonist (Inj. Leuprolide depot 3.75 mg IM once in 21 days x 3-6 cycles) before IVF stimulation improves Clinical Pregnancy rates and decreases miscarriage rates in Infertile women. Endometriosis. (ESHRE Guidelines on Endometriosis Sept 2013)

Once downregulation is achieved, gonadotropins are started, no need to give any agonist during the stimulation. If required, the antagonist may be added if we find increasing LH.

2. Long Agonist Protocols

a) Long Follicular Protocol Agonist (Inj. Leuprolide depot or daily dosage) given from Day 2 of the previous cycle till the day of trigger. Gonadotropin is started from Day2 once downregulation has been confirmed by blood tests (E2/ LH/ P4)

b) Long Luteal Protocol Agonist given from Day 21the of the previous cycle the ill day of trigger, a dose of agonist is halved once gonadotrophins are added.

3. Microdose Flare Protocol - Used in poor responders utilizes the initial flare effect of agonist Initial stimulatory effects- enhances folliculogenesis. Followed by pituitary desensitization

1. Multiple Dose Protocol (Long German –Lubec Protocol)(Inj. Cetrorelix/ Cetrotide/Ganirelix)Half-Life -13 Hours Antagonist injections are given daily – 0.25 mg s.c till the day of trigger

2. Single-Dose Protocol (Short French Protocol) (Inj. Cetrorelix 3 mg s.c) Not yet available in India. The action lasts for 96 hours (3 – 4 days)

Trigger injection is given once ≥ 18 mm follicles of ≥ 3 numbers. Agonist protocol – HCG 5000 IU or 10,000 IU IM or HCG 0.25mg s.c Antagonist protocol1. Inj. Leuprolide 2mg s.c2. Inj. Triptorelin (Decapeptyl) 0.3mg s.c

• Follicular growth allows Flexibility in IVF Programming

• “Batch IVF ”Agonist is less expensive than GnRH Antagonist

• Less ‘Patient Friendly’

• Stressful due to longer treatment cycles (3- 4 weeks for GnRH Agonist)

• Less Safe

• Increased Gonadotropin Dose

• Only Inj. HCG as Trigger

• Increase risk of OHSS

• Costly due to increased Gonadotrophin Expensive Suppression – Slow follicular growth, LPD

• More physiological

• More ‘Patient Friendly.

• Less stressful due to shorter treatment cycle ( 2 wks Vs. 4 wks for GnRH Agonist)

• Decrease Gonadotropin Doses

• Minimal Ovarian Stimulation

• Inj.GnRH Agonist as trigger

• Decrease in OHSS incidence

• Does not suppress raised LH levels in the early stimulation phase (unlike Long GnRH Agonist Protocol).

• Does not allow flexibility in IVF programming in favour

• “Batch IVF” GnRH antagonist is more expensive than GnRH Agonist.