How many matured oocytes are there with all these injections during IVF treatments? That’s the question every patient has in mind before every ultrasound checkup. Statistics show 5~24% patients are what we call “poor responders” as in poor ovarian response after hormonal medication induction.

How to identify a poor responder? There isn’t a specific definition for now, but there are some indexes listed below:

1. less than 2~5 follicles on trigger day (under ultrasound inspection)

2. lower than 300~600pg/ml estradiol value on trigger day (blood serum sample)

3. less than 4~6 oocytes retrieved

4. larger amount of injections or a longer period of stimulating time

5. treatment discontinuity history due to poor response to stimulating

What causes poor response to ovulation induction? Here are some of the common reasons:

1. aging (which leads to diminished ovarian reserve) (most common cause)

2. ovarian surgery history

3. pelvic adhesions

4. endometriosis

5. chromosome abnormalities (such as Turner Syndrome, deletions or translocations)

6. high BMI (often leads to ovarian decline)

It’s crucial for doctors to evaluate ovarian function in order to predict induction outcomes from each personalized IVF treatment. Back in 2006, Dr. Lambalk et al proposed some useful predictions from a series of research: 

1. high FSH value (>12~15mIU/ml) on MC day 2-3 (blood serum sample)

2. high E2 value (>30~75pg/ml) on MC day 2-3 (blood serum sample)

3. low inhibin-B value (<45pg/ml) on MC day 2-3 (blood serum sample)

4. extremely low AMH value

5. antral follicle counts, ovary size, ovarian blood flow, ovary biopsy, ovulation medication/injection tests

Additional Information

• *FSH (follicle-stimulating hormone)

• *MC (menstrual cycle)

• *E2 (estradiol)

• *AMH (anti-Mullerian hormone)

How to tackle this problem of being a poor responder? There is plenty of research on improving ovarian induction outcomes. However, human bodies are not machines. The “perfect” solution isn’t suitable for everybody. But we can try to sort out principles and tendencies from past research, to learn and revise from experiences in order to get not more but better quality oocytes to increase pregnancy possibilities.  These are some of the solutions:

1. Increase gonadotropin injection dosage

This is the most common option. Increasing gonadotropin dosage up to 300~450IU a day seemed effective at first, however recent research shows that no significant improvement on oocytes numbers and pregnancy outcomes by this method. One possible explanation for this is that the number and sensitivity of gonadotropin receptors on each follicle are different. Therefore the effect is limited.

2. Gene recombinant FSH(r-FSH) injections

Many researches show better outcomes using r-FSH injections whether in numbers of oocytes retrieved, mature oocytes, blastocyst quality or pregnancy rate, compared with traditional injection (gonadotropin extracted from urine). But these researches are focused on all IVF cycles, not specifically on poor responders. Also, r-FSH injections are already commonly used clinically.

3. Luteal initiation of gonadotropin injections

Although there were researches that showed more mature oocytes retrieved by this method, it is not encouraged to be applied. The cons are more cycle cancellation rate, lower pregnancy rate, more injections and prolonged induction period, just to name a few.

4. Luteinizing hormone

SISMe.R (an IVF center located in Italy) once studied the effect of FSH injections alongside LH injections, and the result showed that patients with declined ovarian function, poor response to medicine and advanced age might benefit from additional LH injections.

5. Growth hormone

Growth hormone, combined with insulin-like growth factor (IGF-1) produced by liver, seems to increase oocyte maturation rate and quality. Studies also show improvement on clinical pregnancy rate and live birth rate with the help of growth hormone.

6. GnRH (Gonadotropin-Releasing Hormone) agonists

GnRH agonists are applied to mild-stimulating cycles or at the beginning of strong-stimulating cycles by doctor’s orders.

7. Nature cycle oocyte retrieval

Sbracia et al in Italy once conducted a study on 500 poor-responders using nature cycle and found it to be a feasible solution for younger patients.

8. Low dosage of aspirin, male hormone, DHEA, letrozole, etc

Taking additional medication listed above in the hope of increasing antral follicle counts and better response to injections. However, statistics has yet to show a specific result.

9. Early embryo transfer

We tend to transfer day-5 blastocysts which are considered to be healthier embryos for patients with more ovarian reserve. For poor responders, studies show transferring early embryos (day-2/3 embryos) might help with clinical pregnancy rate, minimalizing artificial interference from the lab.

Conclusion

Options listed above are currently for reference only, given the lack of larger scale of research hence no direct proof. And the effect might vary from person to person. At stork, we expect ourselves to be patients’ destination on the journey of becoming parents, no matter how hard the case is. In addition to methods mentioned in this article, we also provide strategies like egg collection, blastocyst collection, and high-efficiency incubation, in order to get oocytes with the best quality. Insemination by ICSI (Intracytoplasmic Sperm Injection), hoping every fertilized egg can divide, multiply and form top-quality embryos. Becoming a mother “as soon as possible and happily” is no longer just a dream.