Difference Between Skeletal Smooth and Cardiac Muscles
Luteaal phase support lifecare centre
1. LUTEAL PHASE SUPPORT IN
ART -- & Recurrent Miscarriages
Dr. Jyoti Bhaskar
Dr. Jyoti Agarwal
Dr. Sharda Jain
Directors -
2. • LPD - 5 - 10 %
• Unexplained infertility - 15- 20 %
• A large fraction of unexplained infertility
may be because of LPD which is difficult to
diagnose
• Recurrent pregnancy loss – 8 -12 %
• 40% of women with recurrent pregnancy
loss may be having LPD
HARD FACTS
3. LPD is characterized by failure to
develop fully mature secretory
endometrium
LPD ----DEFINITION
Decreased progesterone
receptors in endometrium
Inadequate Secretion of
progesterone by Corpus luteum
6. LPD -- Diagnosis
When the luteal phase is shorter than 12 days, it is usually treated
Midluteal progesterone level of less than 10 ng/mL was considered to
be abnormal, the probability of falsely diagnosing LPD was as low as 4%
7. SONOGRAPHIC CRITERIA
•Rupture of follicle < 17 mm
•Poorly formed or ill defined dominant follicle
•Luteinised unruptured follicle
•Lutein cyst formation
•Absence of corpus luteum
•Lack of endometrial echogenicity on 7th
postovulatory day
LPD -- Diagnosis
8. Endometrial biopsy --- was GOLD
STANDARD It is imprecise,
invasive, not reproducible
LPD -- Diagnosis
Currently there is no reproducible, physiologically
relevant and practical clinical standard test to
diagnose LPD
9. • Correction of underlying causes
• Emperical – supplemental progesterone or
HCG
Treatment
Ovulation induction strategies improve fertility by
inducing multiple ovulation and not correcting LPD
10. • Confirmed cases of luteal phase defect
• Unexplained infertility
• Advanced reproductive age
• ART techniques – IUI / IVF / ICSI
• Hyper- prolactinaemia
• All down regulated cycles
• Recurrent pregnancy loss
• PCOS
• Women with strenous exercises and
underweight
Who require Luteal support ?
11. • Supraphysiological estrogen levels may
induce premature luteolysis
• Follicular phase downregulation may impair
luteal phase LH release
• Pure FSH protocols lead to low LH values
• OPU causes granulosa cell disruption
• COH accelerates endometrial maturation
• To overcome any LPD if present
Why in ART Cycles
12. Luteal Phase Insufficiency in
Recurrent Miscarriages
Luteal Phase Support with progesterone
• There is insufficient evidence to evaluate
the effect of progesterone
supplementation in pregnancy to prevent
a miscarriage
(RCOG- Green Top Guidelines2011)
13. • It was only in 2011 that Cochrane meta
analysis suggested that progesterone
supplementation has beneficial effects in
patients with Recurrent Pregnancy Loss.
• It dose, route, frequency & duration does
not effect the outcome
Cochrane 2011 for Recurrent
Miscarriages
15. – PROGESTERONE
– Human Chorionic Gonadotropins
– Estrogen and Progesterone
– GnRH agonist
– Adjuvants
Luteal Support : Drug ?
16. It should be luteomimatic and not
luteolytic
Progesterone is the drug of choiceProgesterone is the drug of choice
Ideal Drug
17. • Promotes secretary transformation of the
endometrium
• It causes local vasodilatation
• Induces uterine musculature quiescence
How Does Progesterone Act?
19. Oral Intramuscular Vaginal
Easy route
Micronized form
Only 10 % absorbs
Not very effective.
First hepatic pass
Side effects like sedation &
hypnosis
P4 in oil base,
Reliable & consistent plasma
level of P4
Rapidly absorb in 2-8 hrs.
P4 level maintain for > 72
hrs.
Difficult & very painful inj
Local reaction & abscess.
Non compliance by pt.
Targeted organ delivery
High conc. In uterus &
endometrium
First uterine pass effect
Minimal systemic side effect
Good Pt. compliance
Self administration, no prick
of needle
Various routes
20.
21. • Immunomodulator
• High affinity for progesterone receptors
• Safe, well tolerated, non androgenic, less
side effects
• Orally active at lower doses
Oral Dydrogesterone
Dose : 20 – 30 mg orally per day
22. • Not too early / not too late – both are
detrimental
• Acceptable window 0f 24 – 48 hrs after
oocyte retrieval / release
• From the same day/next day of IUI
When to Start ?
23. • 300-600 mg / day seen to provide same effect
as with 90 mg of vaginal gel
• Most studies demonstrated equal efficacy
involving 600 mg micronized vaginal progesterone
•25-50 mg of progesterone intramuscularly daily
How much?
24. Not established firmly
Often continued unnecessarily till 12 week
Most evidence based studies suggest to
continue till 9 weeks gestation
How long ?
25. - Optimal route of administration has not
been established
- Equal number of studies support both
vaginal & intramuscular route
- Recent Cochrane review concluded that
no significant difference between different
routes.
Outcome of different studies
remains controversial
26. • Exact mechanism not known
• Single dose of 0.5 mg S/C on 6 th day
after ICSI
• Increases implantation rate, CPR per
transfer, increases live birth rate
Single dose GnRH agonist
Addition of GnRH agonist to progesterone improved
outcome of live birth, clinical pregnancy and ongoing
pregnancy -- Cochrane 2011
27. • Most of the time, luteal cells are
incompetent – HCG is not effective
• HCG supplementation is effective when
specific defect of post ovulatory secretion
of LH exists
Why HCG is not an ideal choice?
10,000 iu for ovulation and then 2500 u every 3-4 days
HCG associated with higher risk of OHSS – Avoid it
( Cochrane 2011)
28. • When GnRH agonist is used as a trigger
• When E2 levels are greater than 2500 on
day of trigger
• All Antagonist cycles
Ostrogen in LPS
29. • Significant effect in favor of Progesterone
• (Dydrogesterone) fares better than micronized
progesterone
• No evidence favouring a specific route or
duration of administration of progesterone.
• HCG, or hCG plus progesterone, was
associated with a higher risk of OHSS. The use
of hCG should therefore be avoided.
Luteal phase support for assisted
reproduction cycles
COCHRANE 2011
30. • Benefit from addition of GnRH agonist to
progesterone
• Overall, the addition of other substances
such as estrogen or hCG did not seem to
improve outcomes
Progesterone seems to be the best option
as luteal phase support,
31. • Abnormal Luteal Phase may occur due to
medical conditions – Thyroid and prolactin
disorders .
• Mid Luteal phase progesterone assessment and
endometrial biopsy are presently being used by
most Gynaecologists for diagnosis of LPD
• No treatment for LPD has shown to improve
pregnancy rates in unstimulated, natural cycles
Take Home Message
32. • CC stimulated cycles – 50% have LPD
but evidence does not support LPS
• ALL PATIENTS OF IUI NEED LUTEAL
SUPPORT
• Micronized Vaginal progesterone at dose
of 200-400 mg /day from day of IUI
Take home message
IUI
33. • IN ART LUTEAL SUPPORT IS A MUST
• VAGINAL progesterone is equally
efficacious and better tolerated than I.M.
preparations
• Adequate dosage – 600 mg must be
prescribed to achieve better outcome
Take Home Message
For IVF - ICSI
34. ADDRESS
35 , Defence Enclave, Opp. Preet Vihar
Petrol Pump, Metro pillar no. 88, Vikas
Marg , Delhi – 110092
CONTACT US
011-22414049, 42401339
WEBSITE :
www.lifecarecentre.in
www.drshardajain.com
www.lifecareivf.com
E-MAIL ID
Sharda.lifecare@gmail.com
Lifecarecentre21@gmail.com
info@lifecareivf.com
&
