Definition of Poor Responder

ESHRE DEFINITION:

At least two of the following three features must be present

  • advanced maternal age or any other risk factor for poor ovarian response (POR);
  • a previous POR; and
  • an abnormal ovarian reserve test (ORT).

Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT

Other Definitions

–Three or fewer recruited follicles or collected oocytes and a serum estradiol concentration lower than 300 pg/mL (if one follicle) or 500 pg/mL (if 2 or 3 follicles) at the time of hCG administration.

–Patients undergoing treatment with ICSI, IVF, or TESE/ ICSI from whom fewer than 5, 6, or 8 oocytes are retrieved.

–be those patients who fail to develop more than three preovulatory follicles after using more than 300 IU of daily FSH or when it requires more than 3000 IU FSH to recruit less than four follicles.

Incidence of poor responder:

It is not very uncommon. Incidence is between 9-24 %. This incidence has wide range , as it depends on individual IVF centre what they define as poor responder.

Data from the ASRM registry showed that 14.1% of initial cycles were cancelled; at least 50% of these were poor responders

CLASSIFICATION OF POOR RESPONDER:

Categorized into two subgroups

those in whom poor ovarian response has been observed in previous stimulated cycles

those in whom poor ovarian response is expected based on ovarian reserve tests or other factors such as age, ovarian surgery,

Etiologies of poor ovarian Response:

Poor ovarian reserve is correlated with advanced maternal age but it can also occur in young female with endometriosis, prior ovarian surgery, pelvic adhesions and smoking.

However, following conditions are also associated with unknown etiologies in young female.

WHAT CAN BE MODIFIED FOR POOR RESPONDERS?

Gonadotropins

Standard dose of gonadotropins is 225IU to 300 IU. Dose are increased in these patients upto 450 IU AND sometimes to 6OOIU. But, different studies showed that even if we increase the dose of FSH, it does not result in better pregnancy outcomes.

Because oocyte retrieval depends on number of basline follicles before stimulation.

GnRH

Long protocols with GnRH agoinst from luteal phase were used previously for lower cycle cancellation and better oocyte retrieval but now it is said in poor responder it causes more suppression ovarian suppression and that could lead to a reduced or absent follicular response.

(i)decrease the length of suppression by decreasing the duration of GnRH agonist use (short and ultrashort, mini- and microdose flareup regimens).

(ii)to lower or to stop (after pituitary suppression) the dose of GnRH agonists initiated during the luteal phase

(iii)to use the GnRH antagonists in combination with gonadotropins to prevent premature LH rise during the mid-late follicular phase.

Alernative approaches:

1. Addition of estradiol in luteal phase.

In a recent meta-analysis of 8 selected studies from 1227 initially searched, the addition of estradiol in the luteal phase with or without the simultaneous use of GnRH antagonist decreases the risk of cycle cancellation and increases the chance of clinical pregnancy in poor responder patients

2. Addition of rLH in addition of rFSH.

Different studies showed that significantly more oocytes were retrieved and significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH treatment in poor responders, suggesting that there is a relative increase in the clinical pregnancy rates of 30% in poor responders.

3. Addition of Androgens:

Studies have shown that taking DHEA for 2-3 months before ovarian stimultions in poor responder increases the oocyte retrieval rate.

1. Addition of Aspirin:

Different metanalysis did not show any significant changes in oocyte retrieval rate or clinical pregnancy rate. Rational behind addition of aspirin is that low dose aspirin increases vascularity and blood flow in oocyte so delivery of Gonadotropins is better.

2. Natural cycle IVF:

Some studies has showed better outcomes of natural cycle in poor responders. But recent studies taking Bologna criteria showed less oocyte retrieval rate and less cumulative pregnancy rate.

3. Oocyte Cryopreservation:

Recently suggested obtaining a large cohort of oocytes in these patients by accumulating vitrified oocytes over several stimulation cycles creating a similar situation as in normal responder patients. According to the results presented in the study, it could be possible to obtain higher live birth rate per patient treated and potentially to reduce the dropout.

Moreover, oocyte cryopreservation can also be used to preserve the fertility of all those women at risk to lose their ovarian potential over the time

 

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