Understanding Your Body’s Response to Fertility Medications During The Stim Cycle

Kristin Shadick

CCO of GoStork

It goes without saying that IVF treatment is intensive in general. Apart from the emotional and physical aspects of the process; keeping up with the various terms (and acronyms, numbers, potential outcomes and more) at every step of the way can get challenging. As always, we are here to help educate new patients by shedding light on key aspects of the journey ahead that are important to understand. One of these elements is that your body’s response to IVF stimulation is unique – and fertility doctors grade patients as ‘High’, ‘Moderate’ or ‘Poor Responders’. Understanding the possibility of these outcomes helps as you may need to consult with your doctor for secondary protocols or changes in medication dosing / timing to promote the most optimal outcome for your body. In this article we’ll explain what it means to be a low or high responder as well as your options based on each situation.

Why are the ovaries stimulated during IVF?

Not all eggs retrieved in an IVF cycle make it to the embryo stage or lead to a successful pregnancy. Because the body only naturally produces one mature egg in each cycle, you’re given medication to harvest as many mature eggs as possible, to increase your chances of success. While most doctors aim to retrieve 15 to 20 eggs per cycle, getting this number is not always possible.

The drugs you’re given and their specific dose is called a protocol and your protocol is personalized based on your age and your levels of Anti-Mullerian Hormone (AMH), Antral Follicle Count (AFC) and Follicle Stimulating Hormone (FSH). Your protocol may be adapted during the stimulation cycle, depending on your estrogen level and the size of your follicles. You can learn more about gonadotropins and other drugs in an IVF protocol in this article.

While your response to the stimulation medication may be predictable to an extent, a ‘High’, ‘Normal’ or ‘Low Responder’ diagnosis is usually made during or after an IVF cycle. Once diagnosed, you may consult with your doctor to identify changes in your protocol for better success in a future cycle. That said, you should also keep in mind that in every cycle, a new cohort of follicles is stimulated. This means that the same protocol may work more successfully in a second cycle. As noted by CoFertility, some reproductive endocrinologists will change the treatment strategy based on the number of follicles available at the start of the cycle. 

What does Low or Poor Responder mean?

Someone whose ovaries and body do not respond to fertility medications is diagnosed as a “poor responder”. About 20% of women undergoing IVF struggle with poor ovarian response. This is associated with high IVF cycle cancellation rates, and low success rates. This diagnosis is usually made after an IVF cycle that results in a poor stimulation outcome and when two of these three criteria are met:

  • Three or fewer eggs were collected on a previous cycle
  • The patient is over the age of 40
  • She has diminished ovarian reserve

A poor response could be due to diminished ovarian reserve (as indicated above), low functional ovarian reserve, obesity, the wrong type of ovarian stimulation, poor injection techniques, and too little ovarian stimulation. 

If you fall into this category, you may be offered a few different treatment options, including:

  • Changes to your stimulation cycle medications. Your doctor may recommend changes to your protocol. Some prefer a mild stimulation protocol, while others opt for a more intensive option to obtain more eggs. A 2017 study found that similar live birth rates were observed with both a mild stimulation protocol and a hyper-stimulation protocol. The researchers concluded that, “considering the higher dosages of gonadotropins and longer stimulation days in patients with hyper-stimulation protocol, it is suggested that poor responders may benefit with the mild stimulation protocol for IVF”. Of course, you should always discuss with your doctor to identify the best protocol for your case.
  • Altering the drugs used for down-regulation (which is the process of ‘turning off’ the ovaries to better control ovulation and egg maturation).
  • More advanced laboratory techniques, such as:
    • Going ahead with the egg retrieval despite the low numbers: If you have diminished ovarian reserve and are not open to using an egg donor at this stage, going ahead with the egg retrieval may be your best option. However, as a poor responder, your chances of achieving pregnancy drop by half as fewer eggs are directly linked to lower pregnancy rates. 
    • Assisted Hatching (AH) to help the embryo expand and implant into the uterine wall. AH has been found to slightly improve clinical pregnancy rates in poor prognosis patients.
    • Day 2 embryo transfers: A study published in Fertility and Sterility found that shortening the length of time prior to embryo transfer may protect the embryo from environmental stresses in the lab and improve pregnancy and implantation rates.
  • Other add ons, such as growth hormone or androgen pretreatment

Normal or Average Responder

You’re regarded as a ‘normal’ or ‘average’ responder if you develop 5 – 8 mature follicles as well as several small ones when stimulated aggressively with injectable FSH.

What does High Responder mean in IVF?

‘High’ or ‘hyper responders’ is a term used to describe women with a high number of oocytes (eggs) retrieved following a standard IVF cycle. It’s still debated whether a high ovarian response is associated with a decreased chance of a live birth when compared to a normal response. A number of studies found that pregnancy and live birth rates in fresh embryo transfer cycles are directly related to the number of eggs retrieved, with a decline in live birth rates at high retrievals. On the other hand, other studies found that a high ovarian response does not compromise pregnancy rates, pointing out that differences in cases and treatment protocols may explain the inconsistent results.

That said, a ‘high’ response comes with its own risks, namely ovarian hyperstimulation syndrome (OHSS). This happens when the ovaries swell and leak fluid into the body. Most cases of OHSS are mild and only cause temporary discomfort. More severe cases of the condition can be life threatening. Thanks to advances in protocols and strategies this condition has become rare. A high response to stimulation can also have an impact on the oocyte and endometrium (although studies on the extent of this impact are very limited).

Women who have polycystic ovary syndrome (PCOS) or have an elevated baseline Luteinizing Hormone to Follicle Stimulating Hormone ratio are more susceptible to exaggerated ovarian response. In addition, multiple studies found that “a large ovarian pool or pre-antral follicles is a significant risk factor for high ovarian response”. In this case, AFC and AMH parameters can be used to predict high responsiveness.

If you’ve been labeled as a high responder and are about to start another cycle, you may want to discuss these strategies with your doctor:

  • Altering your protocol and adjusting gonadotropin doses 
  • Modifying the type of ovulation trigger used
  • Adjuvant therapies, such as metformin if you have PCOS.

Find the best fertility doctor for your care

IVF does not lend itself to a one-size fits all approach, and you should always consult with your doctor to identify the best way forward for you and your unique body. Finding a clinic with experience in the stimulation of low or high responders (depending on where you fit) can help ensure that you get the best care tailored to your specific needs. 

By using GoStork’s platform and concierge service, we can help guide you to physicians that specialize in certain protocols. This may be especially helpful if you find yourself needing a second successful cycle or if you already know you have diminished ovarian reserve. Our Fertility Clinic Marketplace contains in-depth profiles for fertility centers spanning 107 locations across the US. You can view clinics’ experience, costs, and success rates, distilled to your specific case and compared to the national average, and then easily book consultations directly all in our one-stop platform. Ready to research your options? Schedule a free call with our concierge for one-on-one support or start your search for the ideal fertility clinic at gostork.com.