The incidence rate of poor responders (PORs) to stimulation in IVF cycles ranges currently from 7 to 24%. This percent is even higher in patients aged 38 years or older. The main causes are ovarian aging and having a low ovarian reserve.
The good news is that IVF can work for these patients if the cause is found and managed with the most appropriate treatment.
The different sections of this article have been assembled into the following table of contents.
Definition of Poor Ovarian Response
Poor Ovarian Response (POR) is the medical term used for women who are poor responders in IVF cycles. POR is diagnosed after undergoing the egg retrieval procedure.
In order for the specialist to consider that a patient is a poor responder, he will examine the following factors:
- Number of follicles in the ovary
- 5 or less follicles are seen through transvaginal ultrasound in the ovaries.
- Number of eggs retrieved
- If only 3 to 5 eggs have been retrieved. However, organizations such as the Spanish Fertility Society (SEF) consider that a woman is a poor responder if 3 or less eggs are retrieved.
- Stimulation protocol
- When a low number of eggs is collected in spite of having administered a dose of FSH below 3,000 IU.
- Estradiol (E2) levels
- A peak E2 level of <500 pg/ml after a cycle of ovarian stimulation.
The term poor responder is typically used to describe a woman who has undergone at least 2 IVF stimulation cycles which result in 3 or less follicles in each, and whose peak E2 levels are <500 pg/ml after the hCG trigger shot.
These patients need continuous emotional support during their IVF cycle, given that the chances for their cycle to be cancelled are higher for them. In these cases, they have no alternative but to restart the stimulation cycle with an individualized protocol.
The ovarian age does not always match the biological age. Some women are born with an increased number of eggs in their reserve, while others are capable of developing a higher number in each cycle.
POR can be diagnosed after undergoing at least one ovarian stimulation cycle. However, there exist other test that can help determine whether a woman is a poor responder before getting started in order to adapt the stimulation protocol to the special needs of the patient.
There are several factors indicating low ovarian response. The most important ones are:
- Less than 5 primordial follicles seen on ultrasound
- Anti-Müllerian hormone (AMH) below 1 ng/ml
- Basal FSH levels above 10 mIU/ml
- Basal estradiol levels
- LH/FSH ratio
- Inhibin B: levels under 45 pg/ml confirm the existence of a declining ovarian reserve
- Others: clomiphene testing, ovarian volume...
- Diagnosis of POR in previous cycles
High FSH (Follicle-Stimulating Hormone) levels not only indicate POR, but also help predict poor egg quality, which reduces the pregnancy success rate, while at the same time increases the miscarriage rate.
The following are the most common causes of poor ovarian response:
- Age: It is inversely proportional to the ovarian reserve. The older, the harder for them to conceive due to a reduced egg supply.
- Autoimmune disease: Action of FSH receptors (FSHR) in the granulosa cells is blocked by FSH antibodies.
- Reduced ovarian size after undergoing surgery or treatment for endometriosis
- Ovarian aging
The ultimate goal of every IVF cycle is to induce the production of multiple eggs so that a large number can be retrieved and at least one of them is able to result in a viable embryo.
This is precisely the reason why being a poor responder has negative effects on the outcomes of IVF. An insufficient number of eggs available for fertilization diminishes the chances of getting pregnant and increases the probability of cancelling the embryo transfer.
Additionally, POR often leads to eggs of poorer quality that compromise the viability of the embryos at the laboratory, which increases the number of complications for these women.
See this for more: What Is a Good Number of Eggs Retrieved for IVF?
Management & protocols
Fortunately, low responders in IVF have various options to deal with POR and achieve success. Let's find each one of them explained below.
After experiencing poor response during an IVF cycle, it is possible for the patient to start an androgen pretreatment in order to trigger the production of multiple eggs.
It can be done using transdermal testosterone or DHEA (oral dehydroepiandrosterone) replacement therapy. Their effectiveness in cases of PORs, however, has not been proved yet.
Converting an IVF cycle to IUI
If the development of one or two follicles was observed through ultrasound, we may consider the possibility of converting an IVF cycle to Intrauterine Insemination (IUI), always keeping in mind the remaining factors, including the presence of severe male infertility.
IVF flare protocol
In cases of poor response to IVF, a special treatment is typically designed to optimize the chances of success for these patients. The goal is, as always, to get multiple eggs to develop.
An option that is widely used in these cases is the so-called flare protocol, also known as microflare, microdose flare, short Lupron or short protocol.
By doing this, we can take advantage of the initial "flare-up" response of FSH and LH release from the patient's pituitary gland, which normally occurs in the first three days of agonist administration.
Flare-up response: immediate release of FSH and LH at the beginning of the treatment, which effect adds to the ones of the other hormones administered exogenously.
Oocyte accumulation & vitrification
With the purpose of maximizing the number of eggs retrieved and subsequently increasing the number of viable embryos to transfer, several oocyte accumulation cycles can be performed.
Oocyte accumulation means that the eggs retrieved with each cycle are frozen until an optimal amount is available. Then, they are thawed, mixed with the fresh ones that were collected in the last cycle, and fertilized by ICSI.
When multiple IVF cycles have been cancelled due to poor ovarian response, the best option for the patient is egg donation. Egg donors are young, healthy women who donate their egg cells to another woman (the recipient). Donor eggs are fertilized using the husband's sperm in the laboratory.
When the patient has an advanced maternal age, egg donation is a widely used method at all fertility clinics. One should not forget that egg quality diminishes as the woman ages. So, for this reason, for a woman in her 40s or older, the only option to become a mother may be using the eggs of a young girl.
Cost of treatment options for PORs
Another complication derived in cases of poor ovarian response is related to the financial impact of several IVF cycles. This is the reason why selecting the right treatment option is crucial in order to make it as cost-affordable as possible.
The cost of an IVF cycle typically ranges between $8,500 and $12,000 on average. If you opt for a multiple cycle IVF cost plan, you should expect an average amount of about $16,000. This option can be very interesting for poor responders.
On the other hand, only the medications used for the microdose lupron flare protocol can cost up to $5,800 plus the costs of the IVF treatment itself. In case donor eggs were needed, you should expect prices from $20,000.
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FAQs from users
Is the natural cycle a good option for poor responders?
In women who are poor responders, there is medical evidence for similar live birth rates using high dose ovarian stimulation vs. Natural cycle, particularly in younger women. This is presumably because poor responders do not produce many eggs and high does’ stimulation may be detrimental to egg quality. Younger reproductive aged women have the advantage of better egg quality. In older reproductive age women who are poor responders, the option of egg donation is usually much more successful in achieving a live birth. However, the optimal approach to the poor responder is far from certain.
What if the number of eggs I produce is insufficient for IVF?
In order to be able to fertilize more than one egg cell in the same IVF cycle, women's ovaries are stimulated using fertility drugs. The number of eggs required depend on the technique used. For IVF, it is enough with 1 or 2; whilst for IVF/ICSI, we should have around 10 eggs ideally. Oftentimes, due to a varied set of causes, the ovarian response of some patients is inadequate and the number of eggs collected is too low (below 5). In such cases, we can turn to the following strategies:
- To cancel the cycle before egg retrieval and start a new stimulation cycle with a different stimulation protocol.
- To freeze using egg vitrification technique the eggs to collect a higher number of eggs in subsequent cycles.
- To freeze using embryo vitrification technique the resulting embryos in order to transfer 2 in the subsequent cycle.
In short, it depends on the history of each couple.
Can poor responders use supplements to improve IVF outcomes?
Many supplements are used in cases of poor ovarian response to enhance the chances of getting pregnant of these patients, including DHEA, testosterone, CoQ10, human growth hormone (hGH), etc. However, in some cases they work, while in others don't. Again, it depends on the response of each woman and the cause behind POR in each case.
Growth hormone for IVF poor responders, yay or nay?
Some studies have concluded that the use of the Growth Hormone (GH) can increase the clinical pregnancy rates in poor responders to IVF stimulation. However, it may work only if added in the month prior to stimulation with gonadotropins or during the stimulation phase, as it may help increase the number of antral follicles.
Adding GH depends on each patient, and it is often applied in cases of women who have experienced previous IVF failure due to poor ovarian response in spite of maximal doses of gonadotropins.
What's the best IVF protocol for poor responders?
Several studies have been conducted in an attempt to provide an answer to this question. However, no differences in pregnancy rates have been shown between different stimulation regimens. The truth is, each woman's response is different, and so their needs. Hence the importance of personalizing each protocol in order to make the most out of it.
Suggested for you
Ovarian stimulation is a key step in every IVF cycle. Want to learn more about the process? Read: Ovarian Stimulation Protocols for IVF - Process & Medications Used.
A common doubt between IVF patient is related to the number of eggs that should ideally be retrieved for IVF. If this is your case, you may enjoy some further information reading this: What Is a Good Number of Eggs Retrieved for IVF?
The opposite to low ovarian response is having a high response, a side effect of IVF known as ovarian hyperstimulation syndrome or OHSS. Check out this for information: What Is the Ovarian Hyperstimulation Syndrome (OHSS)?
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FAQs from users: 'Is the natural cycle a good option for poor responders?', 'What if the number of eggs I produce is insufficient for IVF?', 'Can poor responders use supplements to improve IVF outcomes?', 'Growth hormone for IVF poor responders, yay or nay?' and 'What's the best IVF protocol for poor responders?'.