ovarian stimulation- back to basicsPresentation Transcript
Ovarian Stimulation Back to Basics Dr Parul Sehgal Incharge IVF, Maharaja Agrasen Infertility and ART centre Maharja Agrasen Hospital, Punjabi Bagh, New Delhi-26
Road to Infertility can be Tough and Tiring
Treatment may involve advanced infrastructure delicate hormone balancing careful handling of gametes
But in the end once inside the mothers body nature take over
END RESULT IS TRULY A NATURES GIFT
1 in 7 couple suffer from infertility
For past few decades more and more nulligravid females are now infertile
Time is critically important factors for couples as AGE is the single most important prognosticator for success
Chance of spontaneous pregnancy in a healthy couple is 30 % in a cycle.
In subfertile couple during the three years after first infertility consultation , chance of spontaneous conception followed by live birth is 25-40%, so in a cycle, fecundity rate is 0.7 – 1%. This drops further by 0.5 if other factors like tubal disease, endometriosis or abnormal sperm parameters are present.
Normally , no ART procedure should be used in a woman below 20 years
No ART procedure shall be done without husbands consent
For a sperm donor , accepted age shall be between 21 and 45 years
To look for the cause
Female Factor Male Factor
Anovulatory Infertility WHO CRITERIA
GP I :- FSH, LH Dysfunction at the level of hypth. & Pit
GP II :- (N) FSH
GP III :- Ovarian Failure FSH
GP IV :- Prolactin
GP V :- Out flow tract defect.
WHO GP II
Most commonly found
All PCOS present with this type of anovulation
Oligo Ovulation:- Ovulation once in 35-180 days
2) Anovulation:- No ovulation for 6 months
3) Hyper androgenism :- Clinical signs
blood test for S.Testosterone
Free androgen Index
4) Oligo menorrhea
CHECK THE OVARIAN RESERVE
Basics of ovarian stimulation
Baseline FSH :- (Blood Test)
Antral follicular count (USG)
FSH >10-20 Poor Response
LH >10 Poor Response
E2 >60-75 Poor quality OOcyte
Insulin B normal 45pg/ml
<45 pg/ml-Low reserve
USG : Antral follicle count more practical & direct approach.
Superier to chronological age & endocrine markers
-Eijkemans et al
B/L Ovarian <10 Follicles - Poor Response
Contd…) On the D2/3 of cycle
Normally follicular size at D2=3-5mm
E2 high E2 Low
Functioning Ovarian cyst Non Functioning ovarian cyst
Rest the Cycle You can proceed
cyst may regress OR Poor ovarian response New follocle may develop
Dose for normal women 50-100 mg/day
less sensitiveUpto 250 mg/day
Extremely sensitive 25 mg/ day
No advantage in using dose > 150 mg
Start with 100 mg will reduce the Tt time
75% of pregnancies occur with in first 3 cycles
80% will ovulate
30-45% will get pregnant
20-25% will not respond at all
Can be started on Day 2/3/4/5
does not influence results
Clomiphene as a choice
Mainly in Irregular ovulation WHO type II , PCOS
In ovulating women with Unexplained Infertility
CC+ IUI – Increase pregnancy rates
CC may overcome subtle defects in ovulatory functions, inc the no. of mature follicles.
Why my patient did not respond to CC
Obese BMI high
Persisting luteal cyst
WHO gp I anovulation- Abn Hypoth./Pituitary
WHO gp III anov - premature ovarian failure
WHO gp IV anov - High prolactin
What can be done
Insulin sensitizing agents-Metformin
Addition of Cabergoline/bromocriptene
Sequential CC + Gonadotropin
Aggressive weight loss
Extended Clomiphene therapy stair step protocol
Day 3-7 Begin CC 50 mg/day
Day 7-14 USG Follicular study
Day 14 Small Follicles
Day14-18 CC 100 mg/day
Day 19 USG Follicular Study
Day 22-26 CC 150 mg/day
Total time stairstep protocol 28 days
Traditional protocol 88 days
Side effects of Clomiphene
Bloating & abdominal distension
Ovarian cyst formation
Hot flashes( DISTURBED SLEEP) 10%
Visual disturbances 5%
blurred vision , flashes of light
Dose 2.5 to 5mg/day for 5 days
Start on cycle day 3/4/5
No effect on cervical mucus or endometrium
Many trial have proved letrazole giving more pregnancies when used alone or with gonadotropins
Still evidence–based medicine is needed to use it as first line of treatment
Stimulated with CC/Letrazole IUI Anovulation/ Irregularovulation For Better Results
Indication : Women with regular (25- 32days) ovulatory cycles & patent Fallopian tubes.
Male partner must not have severe male infertility <5X106 motile sperm/ml. Mild to moderate male factor is not excluded &these couples often conceive readily.
Not meant for:
Women with short cycle (<25 days) & FSH >12 iu/l
Women with Normal FSH but LH 10 iu/l
Woman with irregular cycles & severe anovulation
Women with raised basal FSH & LH >8iu/l
Women with H/o severe endometriosis
Women with H/o abdominal surgery
Women with partner with severe male factor unless using donor sperm.
HOW DOES IUI HELP
Treatment is designed to
Synchronise the timing of ovulation & sperm deposition
Marginally increase the number of oocytes available for fertilisation
Place the sperm in a closer approximation to the oocyte
Over response with ovarian stimulation for IUI
>3 FOLLICLES >16 mm
follicle reduction / cont. to IVF
Next attempt IVF: Long protocol
IUI IN OLDER AGE GROUPS
# Older women needs more aggressive stimulation >39.
# Although occasional pregnancies will occur if older women are treated with SIUI, this will waste critical time for the majority.
27yrs old female.
Married for 3 years
Attempting for 16months.
No. contraception taken
Regular menses , mild dysmenorrhea that responds to NSAIDS.
Physical ex:- no cervical/adnexal tenderness.
Vaginal/ semen culture- negative for infection.
Priliminary test Day 3 :- FSH,LH
What other test
Rt. Sided proximal tubal obstr.
Lt. sided patent Tube.
2) Tubal Obstr
Tubal flushing Saline Sonography IUI
6 Cycles of Clomiphene citrate
Failed to Conceive
Laparoscopy IUI with gonadotropins
Reveals ext. Adhesion with endometriosis.
Laprotomy with With severe endomertriosis
Lyses of adhesion & ext. adhesion IVF-ET offers
& resection/ablation best pregnancy rates &
Of endometiosis avoid risk of surgery .
2 yrs of sec. Infertility
O.C for 5 yrs
Stopped O.C 2yrs ago.
She presented to her gynecologist
5 months ago with c/o infertility.
Test offered: D3 :- FSH
Aggressive workup needed considering (her age)
2 cycle of CC with timed intercourse
Do you encourage CC with Gonadotropin HSG/
More cycle of CC IUI With IUI Laparoscopy
With timed intercourse?
3 more cycle of IUI with CC
Failed to become pregnant.
HSG Laparoscopy Gonadotropinc
B/L patent tube with no intrauterine fllling defect.
Patient became pregnant in the second cycle of IUI
Pts Age 44yrs Male partner-49 yrs
ML 17 years
P0A1 last abortion 7 years back, 5wks gestation
HSA Tmc 70 million, 43 % Am
HSG (2007) B/l tubes patent
FSH 28 mIU/ml
LH 12 mIU/ml
She has had 3 IUI’S IN THE LAST 6 MONTHS
Few Laparoscopy IVF-ET
more and with
IUI’s hysteroscopy donor Oocyte/ Embryo
+ IUI + Gonadotropins
As treatment revolves around these basic parameters,we have answers for all our failures and as we work on our patient, we know