ART in Endometriosis

1. Stage III and IV endometriosis

2. Altered tubo-ovarian relationship

3. Multiple failed IUI

4. Age factor of the female

5. Associated male infertility

1. Lower ovarian response to Gonadotropins

2. Poor response – 29.7% required to discontinue the cycle

3. Lower number of oocytes retrieved

4. Poor oocyte and embryo quality

5. Decreased fertilization and cleavage rate

6. Decreased implantation rate

7. Release of embryotoxic substances from endometriotic implants

Controlled ovarian stimulation with both GnRH-a and GnRH antagonist protocols 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. When the outcome of subsequent freeze-thaw cycles is considered, the cumulative fecundity rate will be higher in the agonist protocol.

GnRH Agonist (Inj. Leuprolide depot 3.75 mg IM once in 21 days x 3-6 cycles) prior to IVF stimulation improves Clinical Pregnancy rates and decreases miscarriage rates in Infertile Women with 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

a) Long Follicular Protocol

Agonist (Inj. Leuprolide depot or daily dosage) given from Day 2 of the previous cycle till the day of trigger

GnRH is started from Day2 once down-regulation has been confirmed by blood tests (E2/ LH/ P4)

b)Long Luteal protocol

Agonist given from Day 21 of the previous cycle till the day of trigger, the dose of agonist is halved once GnRH are added

> Used in poor responders

> Utilizes the initial flare effect of agonist

> Initial stimulatory effects- enhances folliculogenesis

> Followed by pituitary desensitization

(Inj. Cetrorelix/ Cetrotide/Ganirelix)

Half-Life -13 Hours

Antagonist injections are given daily – 0.25 mg s.c till the day of trigger

(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 rHCG 0.25mg s.c

Antagonist protocol

1. Inj. Leuprolide 2mg s.c

2. Inj. Triptorelin ( Decapeptyl) 0.3mg s.c

> Synchronous follicular growth

> Allows Flexibility in IVF Programming

> Favours “Batch IVF ”

> The Agonist is less expensive than GnRH Antagonist

> Less ‘Patient Friendly’, stressful due to longer treatment cycles

> ( 3- 4 wks for GnRH Agonist )

> Less Safe *Increased Gonadotropin Dose

> Only Inj. HCG as Trigger

> Increase risk of OHSS

> Costly due to increased Gonadotrophin cost

> LH 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)

> Safer

> Decrease Gonadotropin Doses

> Minimal Ovarian Stimulation

> Inj.GnRH Agonist as trigger

> Decrease in OHSS incidence

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

> Does not allow flexibility in IVF programming

> Does not favour “Batch IVF”

> GnRH antagonist is more expensive than GnRH Agonist