Step up protocol for IUI

 

Step up high dose protocol in IUI cycles under the umbrella of an ART center à the provision of conversion to IVF should be there and also provision of treating OHSS if such an unfortunate event arises.

1)          Indications of step-up? :- 1) WHO Group II Anovulatory PCOS who are resistant to CC or failing to conceive with CC despite ovulation.

2)          Advantages? Why Low dose step up? The purpose is to achieve monofollicular growth, thereby avoiding multiple pregnancies and also minimize the incidence of OHSS.

3)           Inclusion criteria:      Who are suitable? 1) She must have been tried at least 3 cycles of OI with 100 mg of Letrozole / CC .  2) WHO Group II women-PCOS women-with Chr anovulation as was diagnosed by amenorrhea/oligomenorrhea/ or women with regular cycle length but anovulation was documented by serum P assay in cycle length of 21-35 days.

3) Infertility of at least 1 year, BMI 19-30 kg/M²

4) At least one tube must be patent.

 5) TVS- exhibits normal pelvic anatomy

6) Day 2 FSH ranging from 1-12 IU/Lit

7) Normal Prolactin & total Testosterone

8) Normal semen/ Donor semen

   9) Signed informed consent.

4)          Exclusion criteria:-A) More than 12 unsuccessful OI by letrozole /CC or combined letrozole and CC in a single cycle B) persistent Ov cyst> 10 mm on day 3 . C) Ovarian endometriomata D) To keep a gap of at least 1-2 months –after previous CC. This is not applicable for letrozole. E) May supplement metformin, gonadotrophins F) Cong malformations of genital organs.

5)          Treatment Efficacy:-How effective is low dose step-up protocol ?

In WHO Group II Anovulatory PCOS who are resistant to Letrozole / CC . or failing to conceive with CC despite ovulation? –

6)           Outcome :-As many as 50% of women will achieve monofollicular growth. Rest 50% won't respond favourvbale , They be planned for ART by antagonist cycle or long down regulation àIVF ET

7)          Dose schedule? Initiation:- by starting with HP-FSH 75 IU daily subcut from day (  day 2 – to day 5, on any day , may be initiated after Progesterone  withdrawal as well) . This kind of HP-FSH is available as powder with solvent-to prepare for soln. The prepared solution will be 1 ml for both HP-FSH/R-FSH subcut. For r-FSH pen system is available like insulin pen.

 

8)           For first 7 days such dose of 75 units is to be  maintained and looking at response after 7 days of 75 i.u. of G’trophin à then dose should be  increased by another 37.5 i.u. Any dose change must be maintained for at least 7 days in that schedule. Maximum dose was 225 iu per day and maximum daily dose  of Inj must not exceed 225 iu  per day . Very Rarely as long as 6 weeks may be warranted.

 

9)          When to stop Gonadotrophins & go for trigger? A) at least one follicle must be  > 17 mm

B) two-three follicles were > 15 mm. C) if there is no response after as long as 6 weeks of Gtrophin Ry.

10)  Trigger by which agent?- HCG 5000 iu by subcut   -i.m.- and serum Progesterone is to be assessed 9 days after hcg as no luteal support was implemented.

 

11)  When not to push trigger?  If no. of follicles > 4 follicles above 15 mm in diam and or E2 > 2000 pg/ml and cycle is planned for IUI to avoid multifetal pregancy & OHSS .

12)   Luteal support-a necessity in IUI cycles ? :- Though many are of opinion that  Luteal support is desirable (vaginal micronized progesterone ) still there are some who don’t prescribe luteal support ..

13)  Definition of CC resistance women? If after 3 cycles of 100- 150 mg of CC is administerd or letrozole 2,5 or 4 mg Od is administerd  and there is no growth of follicle that condition is termed as Letrozole or Cc resistant cases .

14)  Conclusion:- U-p-FSH was not inferior as a method of OI  in ) WHO Group II Anovulatory PCOS who are resistant to CC: FM is essentialà to note no & size of follicles.  & alt. day Serum E2 estimation.  The effective dose of gonadotrophins required in each cycle to have a response must be recorded so as to plan the future stimulation.