Step up protocol in non down regulated cycles

 What is Step up high dose protocol in letrozole /CC resistant women?

What we need to know regarding step up gonadotrophin protocol?? When indicated? 

Ans: In letrozole /CC resistant women before ART procedure is finally adopted but Chr step up should always be accompanied by IUI procedure.

Where to be supervised?? Where such procedure should to be done?? ::

Condition 1: Where to be dome??  This protocol should ideally be done at an ART center where Ovum Pick Up facility is existent or a center where a nearby such ART center exists with provision of treatment of severe OHSS exists. This protocol described herein is in non-down regulated cycles.

Condition 2:-This protocol is not to be confused with Chronic low dose protocol where initial stimulation is with either HMG or r-FSH either 37.5 IU or 50 IU - to start with and continued at such dose for at least 10 days .Only after 10 days first scan is done and if no growth of  follicle > 10  mm  is imaged then the  dose is increased to 75 IU again for 5-7 days (Concept of threshold dose )

 

Condition  3 : What do we mean by Threshold dose??

The threshold dose is the initial dose to which resting follicles respond to call of gonadotrophin. This threshold dose varies  from women to women , While some may respond to  even a small dose   37.5 IU( good responders—Normo responders)  but  some may need even 100  IU to respond initially (poor responders) !! . This dose can’t be predicted well ahead though high AFC, high LH and high AMH call for initiation of in case of Chr low dose as low as 25/ or even 37.5 IU initially if AFC & AMH arte on higher percentiles (for Chr low dose only) But for “Step Up”- the initial dose is usually 75 though sometimes 50 iu / 62.5 IU is used from day 3.  But by and large for average cases 75 iu  is used though some experts initiates with 75 IU at the outset (day 3-mind you dear members these are non down regulated cycles i.e. is no pretreatment with agonist  initiated  from in late luteal phase day 21 of previous cycle ).

 By contrast in ART (IVF) the starting dose is often 150-225 IU because multifollicular development (superovulation) is the aim and IVF specialists intend to pick up as many as MII oocytes as possible. But in step up with IUI one follicle  at best 2 follicles are desirable , In case there are 4 follicles grow up to 16 mm then either  Plan of IU is cancelled or the cycle is converted to IVF .(no cycle cancellation)

Why low dose to start with ??

This is indicated only for  cases with PCOS-as in PCOS women they contain as many as 6 times more number of FSH sensitive antral follicles in their cohort.:- This threshold dose varies from one PCOS women to other Believe this old man or not , but fact is even in the same woman the initial  dose of threshold dose may vary in different cycles!!

Indications of step-up?

1)              WHO Group II Anovulatory PCOS who are resistant to CC or 2) failing to conceive with Letrozole/CC despite ovulation.

2)              Inclusion criteria

1.              Anovulatory infertility

2.              Age 18 - 39 years

3.              Anovulation with oligomenorrhoea (> 35 days of mean cycle length) or amenorrhoea

4.              Normal serum FSH (< 10 IU/l)

5.              Two ovaries

6.              BMI < 35

7.              First FSH/HMG cycle at the Fertility clinic.

Who are suitable? (contd)

A sperm sample compatible with conception or semen from a donor. Tubal patency documented by either hysterosalpingography (HSG) or hysterosalpingography by ultrasound (HSU) in cases where the woman has had a pelvic infection or pelvic surgery.

She must have been tried at least 3 cycles of OI with Letrozole 5 or 7.5 mg / 100 mg of CC.  2) WHO Group II women-PCOS women-with Chr anovulation as was diagnosed initially by amenorrhea/oligomenorrhea/ or women with regular cycle length but anovulation was documented by serum P assay in cycle length of 21-35 days.

Infertility of at least 1 year, BMI 19-35 kg/M²

At least one tube must be patent (prior HSG must before costly Gonadotrophin and detailed monitoring expenses are borne) .

TVS- exhibits normal pelvic anatomy in pre G’dotrophin cycle).

Day 2 FSH ranging from 1-12 IU/Lit

Near normal Prolactin & total Testosterone

Normal semen/ Donor

Signed informed consent.

8.               

Exclusion criteria

 

1.              A history of >12 ovulation induction cycles without achieving pregnancy.

2.              More than three earlier gonadotropin cycles at other clinics or earlier treatments with threshold doses below 75.

3.              Known hyperprolactinaemia or any other endocrine disturbance or systemic disease of the pituitary gland, thyroid gland, adrenal gland, pancreas, liver or kidney.

4.              Undiagnosed vaginal bleeding.

5.              Acute or chronic infection with HIV or hepatitis.

6.              Persistent ovarian cysts or endometriomas detected by ultrasound.

7.              Tumors of the hypothalamus, pituitary gland, breast, adrenal gland or ovary.

8.              Pregnancy or lactation.

9.              Current or past alcohol or drug abuse.

10.   A history of chemo- or radiotherapy.

11.   Malformations of reproductive organs incompatible with pregnancy.

Hypersensitivity to any trial medication