Drugs used in IVF
- Aromatase inhibitors(Letrozole)
- Dopamine agonist
- Insulin sensitizer
- Most widely used
- Simple to use
- Minimal side effect
- Cost effective
- Starting day of treatment ,whether on day 5 of the cycle does not influence results.
- Less then 50% of patients response to 50 mg so 100mg seems to be a more ideal starting dose.
- >150 mg does not significantly increase the ovulation rate
- Letrozole is a third — generation aromatase inhibitor which came in for the treatment of estrogen positive breast cancer.
- Due to it antiestrogenic action , it use is extended to ovulation induction too.
Aromatase inhibitors act directly on the ovary to decrease production of estrogen by competitive , reversible binding to the aromatase receptor –thereby therapy increasing, *GnRH secretion,
- pituitary LH & FSH production &
- ovarian follicular development
- 2.5 mg once daily X 5 days (D3-7 of menstrual cycle); for 3 consecutive cycles or till occurrence of pregnancy
- > 3 courses of therapy not recommended
- Dosage or duration of therapy ..2.5 Or 5 mg/day for 5 days …..many trials undertaken…showing comparable pregnancy rates….while other study showed no advantage
- A study showed a single dose of 20 mg letrozole had comparable pregnancy rates as 2.5 mg given from 3 to 7 days with or without gonadotrophins.
- Day 1 — 2.5 mg
- Day 2 — 5 mg
- Day 3- 7.5 mg
- Day 4 -10 mg
Results have shown that this protocol when adopted has led to ovulation in CC resistant PCOS & have pregnancy rates comparable to the FSH employed group
In our experience , we have seen side effects that are similar to those seen with clomiphene citrate
- Hot flashes
- Breast tenderness
- Better pregnancy outcomes & higher live births compared to CC in PCOS patients
- Effective even in patients with CC-resistant PCOS
- Reduces Gn dose & superior alternative to CC in combined Gn cycles
- Monofollicular development &b multiple pregnancies
- No anti-estrogenic effects on endometrium & cervical mucus
- Lower cycle cancellation & risk of hyperstimulation
- Safety established in clinical studies.
- rFSHVs other GN (HMG, hp-FSH, p-FSH)
- No evidence of difference in LBR or OHSS
- 42 trials, 9606 couples
- Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety
- (Cochrane Database Syst Rev. 2011, Wely et al) Use either u or recGntfor ovarian stimulation(NICE, 2013)
- Produced byModification of the native GnRHdecapeptideat 6 & 10 positions
- Therapeutic uses in IVF:
- Down regulationTo block LH surge To prevent premature lutenization
- Triggering in antagonist protocol
- Effects of GnRha
- Flare effect: Within 12 h and lasting 24-48 h: 5 fold increase of FSH10 fold rise in LH & 4 fold elevation in E2.
- Continuous administration: opposite effects:internalization of the agonist /receptor complex & decrease in the number of receptors (down-regulation). : paradoxical suppression of the pituitary Gntsynthesis & liberation (desensitization).
- The decreased levels of FSH & LH: 1. Arrest of follicular development 2. Decrease in sex steroid levels to castrate levels.
- The pituitary blockade persist during agonist ttbut it is reversible after therapy.
- Produced by Modification at 6, 10, & 1, 2, 3, 8 positions
- Effects Inhibition of LH & FSH immediately without the initial flare up effect of the Gnta.
- Mechanism of actionCompetitive receptor blockade. The suppression of LH is dose related. Larger doses of antagonist is associated with marked reduction of pregnancy rate in IVF cycles
- LPD in infertility
- LPS in IUI
- LPS in IVF
- Endometrial preparation
- To block LH in COS
Estradiolvalerate: 2 mgWhite tab in Cycloprogynova
While it was initially accept as a first line treatment in anovulatory PCOS, ACOG guidelines (2003) (WU placed it as the second drug to be added to clomiphene if clomiphene fails to give baby as first line induction agent
The Canadian guideline of 2010 stated that metformin combined with clomiphene citrate may increase ovulation rates & pregnancy rates, but does not significantly improve the live birth rate over that of clomiphene citrate alone .
* Metformin may be added to clomiphene citrate in women with clomiphene resistance who are older & who have visceral obesity.
Cochrane review (2012) indicated that metformin was not effective in inducing ovulation alone or in relation to clomiphene ,but it was capable of increasing the pregnancy outcome . It concluded that the role of metformin in improving reproductive outcome in women with PCOS appears to be limited
The Thessaloniki ASRM / ESHRE guidline (2008) emphasized the same & restricted its use to PCOS patients where there was a glucose intolerance noted . *It is also indicated that it was helpful in reducing the incidence of OHSS & missed abortion .