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Causes of Poor Ovarian Response – Treatment Protocol

Despite breakthroughs in reproductive technology, poor ovarian responders continue to pose a problem to clinicians around the world. With an increasing number of women falling into this category, it is essential in developing and execute treatment options intended to improve pregnancy rates in these women.

In-vitro fertilisation treatment aims is to stimulate the ovaries for multi-follicular development compared to natural menstrual cycle, in which a single dominant follicle emerges from a cohort of 10-20 follicles recruited for that cycle. As a result, there are more fertilizable oocytes available, resulting in more embryos for transfer.

According to their ovarian response to Gonadotropin stimulation, women can be categorised into high, intermediate, and poor responder types. As a matter of fact, the poor responders have a considerable impact on IVF success rates and require a unique approach in order to achieve the desired results.

Concerns of Poor Ovarian Responders

  • Poor Ovarian Responders are women who:

  • Do not have a sufficient reaction to IVF stimulation

  • Have a lower yield of embryos, and

  • Have a lower IVF success rate due to a decrease in the Cumulative Pregnancy Rate (CPR)

This signifies:

  • Inadequate folliculogenesis causes cycle cancellations

  • Several unsuccessful cycles

  • Increased number of attempts to start a family

  • More treatment expenses

  • Aneuploidy increases, resulting in low embryo quality and failure to implant

  • Pregnancy chances are significantly reduced

Because oocyte yield is so important to IVF success, it was crucial to identify the category of women who don't respond well. These are the poor ovarian responders, or women who don't produce enough fertile oocytes of good quality. Many criteria have been used to characterise these women over the years. Ovarian reserve, CC challenge, GnRH, GnRH agonist, assessment of Anti-Mullerian hormone (AMH) and antral follicular count (AFC), FSH and E2 levels, cycle cancellation rate, and gonadotropin dose have all been used as screening tests to determine the ovarian response to ovulation induction.

Poor responders were defined in a variety of ways, but the most common ones were:

  • Advanced maternal age

  • Previous cycle cancellations in the past

  • Low ovarian volume and/or ovarian cancer

  • Reduced AFC

  • In a prior round, there was a poor response.

  • FSH Basal Parameter is abnormal

Poor Ovarian Response Risk Factors

There have been other risks variables discovered that may indicate a poor response to ovarian stimulation in younger women, in addition to advanced age and decreased ovarian reserve. Poor Ovarian Reserve can occur in younger women for a variety of causes. These are:

  • Poor Ovarian Reserve in women at a younger age

  • Unexplained infertility

  • Single ovary

  • Previously performed ovarian cystectomy

  • Habitual smoking

  • Chemotherapy and/or radiotherapy treatment performed in the past (for cancer survivors)

  • Auto-immune response

  • Premature menopause in the family, X chromosomal derangements, and fragile X mental retardation 1 (FMR1) pre-mutation are all genetic risk factors

Challenges of Poor Ovarian Reserve

Women who have a poor response to IVF stimulation are more likely to have their cycles cancelled. Patients are usually discouraged by this because IVF causes significant physical, mental, and financial stress.

Treatment cancellation due to low ovarian response has been reported to be a serious concern in 12-30 percent of all stimulated cycles. Because so few oocytes are recovered, these women's total pregnancy rates are far lower than normal responders. Another issue that arises regularly is the increased risk of miscarriage, even if pregnancy is achieved.

The loss of primordial follicles with age has been associated to a loss of oocyte quantity and quality, which is a primary cause of poor ovarian response. Poor oocyte quality leads to poor embryo quality, which has an impact on the treatment outcome.

All of the above factors combine to produce a population with a very low Live Birth Rate.

Treatment Options for the Poor Responders

IVF treatment attempts to increase the number of follicles available for recruitment in the IVF cycle because the outcome of IVF is determined by oocyte yield. Because this set of follicles will be available at the pre-antral stage, therapy usually begins around 2 months before IVF begins. Follicles are less likely to respond once they reach the antral follicle stage. Androgens like testosterone and DHEA supplements are used as part of the pre-treatment strategy.

High-dose gonadotropins can also help poor responders. High doses of >300 IU, on the other hand, are unlikely to be useful and should be avoided.

For the poor responder, the lengthy procedure is still one of the best options. The overall success of the gonadotropin can be improved by lowering the agonist dose at the start.

The antagonist protocol is also a popular treatment option because it uses less gonadotropin and has a shorter stimulation time with equivalent results.

Poor responders can potentially benefit from the brief or microdose flare treatment. When utilising this approach, pretreatment with OCP's is recommended.

In the double stimulation treatment, two IVF stimulations are performed in one menstrual cycle. This causes follicles from both the follicular and luteal phases to be recruited.

After many IVF cycles with subsequent embryo banking and transfer of an adequate number of good quality embryos, another approach by which women might improve their pregnancy rates is egg accumulation and embryo pooling.

Last but not least, history-taking and investigations are an important part of treatment. When a woman is diagnosed as a poor responder, it's essential to figure out why. A poor response to IVF can be caused by a variety of factors, including a misdiagnosis, inappropriate drug administration, protocol selection, insufficient drug storage, and obesity. These should be taken into account and controlled appropriately at all times.

Hope for Us

Women who have had a poor response to IVF are becoming a more common group of patients who require IVF. They are resistant to treatment, but with the right assessment and protocol, IVF can be quite successful, especially for those who are younger. They should be thoroughly counselled, and the dangers and benefits of their actions should be explained. More recent studies will aid us in improving therapy options for this group of women.

- Dr. Girija Wagh


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