IVF Treatment and Poor Responders – an Interview with Dr. Ruth Sánchez

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Poor ovarian response, a condition where a woman’s ovaries exhibit limited responsiveness to standard ovarian stimulation protocols during IVF cycles, presents a formidable barrier on the path to conception. It’s a multifaceted phenomenon influenced by a myriad of factors, including age, ovarian reserve, genetic predispositions, lifestyle choices, and underlying medical conditions. Despite advancements in reproductive medicine, poor responders grapple with uncertainties and complexities that warrant a nuanced understanding and tailored approach to treatment.

Dr. Ruth Sánchez, a leading expert at the Fertility Clinic UR Vistahermosa in Alicante, is here to guide us through this complex terrain. In this article, she answers key questions about poor responders in the world of IVF, providing clarity and reassurance to those navigating this often perplexing aspect of fertility treatment.

poor responders IVF options IVF Treatment and Poor Responders - an Interview with Dr. Ruth Sánchez

What exactly does it mean to be a “poor responder” in the context of IVF treatment?

In the context of an in vitro fertilization (IVF) treatment, a “poor responder” refers to a woman whose ovaries do not respond well to the standard ovarian stimulation protocol used during IVF cycles. This means that, despite receiving high doses of follicle-stimulating hormone (FSH), the ovaries produce a lower number of follicles than expected.

What are the main factors that contribute to being classified as a poor responder?

Several factors can contribute to being classified as a poor responder in the context of IVF treatment:

  • Advanced Age: As women age, their ovarian reserve declines, meaning they have fewer eggs of lower quality. Advanced maternal age is commonly associated with poor ovarian response.
  • Diminished Ovarian Reserve (DOR): This refers to a decline in both the quantity and quality of a woman’s remaining eggs. It can occur at any age but becomes more prevalent as women get older. DOR can result from various factors, including genetics, lifestyle factors, previous ovarian surgery, or certain medical conditions.
  • Ovarian Surgery or Damage: Previous ovarian surgeries, such as ovarian cyst removal or endometriosis surgery, can reduce ovarian reserve and impair ovarian function, leading to a poor response to ovarian stimulation.
  • Genetic Factors: Some women may have genetic predispositions that affect ovarian function and response to fertility treatments.
  • Previous Ovarian Stimulation Cycles: Women who have undergone multiple IVF cycles and have had poor response in previous cycles may continue to experience poor response in subsequent cycles.
  • Lifestyle Factors: Smoking, excessive alcohol consumption, obesity and a poor diet can negatively impact ovarian function and response to fertility treatments.
  • Other Medical Conditions: Certain medical conditions, such as autoimmune disorders or cancer treatments, can affect ovarian function and response to ovarian stimulation.
  • Environmental Factors: Exposure to environmental toxins and pollutants may also influence ovarian function and response to fertility treatments.
  • Individual Variability: Each woman’s response to ovarian stimulation can vary based on individual factors and what constitutes a poor response for one woman may not be considered the same for another.

How common is it for patients to be classified as poor responders in IVF treatment?

The prevalence of poor ovarian response in IVF treatment varies depending on several factors, including the population being studied, the criteria used to define poor response and advancements in IVF protocols and technologies. Generally, poor ovarian response is estimated to occur in approximately 9% to 24% of women undergoing IVF treatment.

However, it’s important to note that the definition of poor ovarian response can vary among fertility clinics and researchers. Some clinics may use specific criteria, such as the number of follicles produced or the quantity of eggs retrieved, to classify patients as poor responders, while others may consider additional factors such as age and ovarian reserve testing results.

What specific challenges do poor responders face during the IVF process?

Poor responders in IVF treatment face several challenges throughout the process, including:

  • Low Ovarian Response: The primary challenge is the inadequate response of the ovaries to ovarian stimulation medications. Poor responders typically produce fewer follicles and eggs, reducing the chances of successful fertilization and embryo development.
  • Lower Egg Retrieval Rates: Due to the limited number of follicles and eggs, poor responders may have fewer eggs retrieved during the egg retrieval procedure compared to women with a more robust ovarian response. This can decrease the number of embryos available for transfer and freezing, limiting treatment options.
  • Decreased Pregnancy Rates: Poor ovarian response is associated with lower pregnancy rates in IVF treatment cycles. Even if embryos are successfully transferred, the reduced number and quality of embryos may decrease the likelihood of implantation and successful pregnancy.
  • Increased Treatment Cycles: Poor responders may require multiple IVF cycles to achieve a successful pregnancy, leading to increased emotional, physical, and financial burdens. Each cycle involves additional medications, monitoring appointments, and procedures, prolonging the overall treatment process.
  • Emotional Stress: The uncertainty and disappointment associated with poor ovarian response can lead to heightened emotional stress and anxiety for patients. Facing multiple treatment failures and uncertain outcomes can take a toll on their mental well-being.
  • Financial Considerations: The cost of IVF treatment can be substantial, and poor responders may incur higher expenses due to the need for multiple treatment cycles. This financial burden can add to the stress of the IVF process.
  • Decision-Making Challenges: Poor responders may face difficult decisions regarding whether to continue with further IVF attempts, explore alternative fertility treatments, or pursue options such as egg donation or adoption.
  • Limited Treatment Options: Despite advancements in IVF protocols, some poor responders may not respond adequately to standard treatments. We may need to explore alternative stimulation protocols or adjunctive therapies, but success rates may still be lower compared to women with a more favorable ovarian response.

Are there any predictive tests or indicators that can determine if a patient might be a poor responder before starting IVF treatment?

Yes, several predictive tests and indicators can help us, the clinicians, assess the likelihood of a patient being a poor responder before starting IVF treatment. These tests can provide valuable information about a woman’s ovarian reserve and potential response to ovarian stimulation. Some of them includes:

Ovarian Reserve Tests:

  • Antral Follicle Count (AFC): AFC is determined through transvaginal ultrasound and measures the number of small follicles present in the ovaries at the beginning of the menstrual cycle. A lower AFC may indicate a reduced ovarian reserve and a higher likelihood of poor ovarian response.
  • Basal Follicle-Stimulating Hormone (FSH) Level: Basal FSH levels are typically measured on the third day of the menstrual cycle. Elevated FSH levels may suggest diminished ovarian reserve and a higher risk of poor ovarian response.
  • Anti-Müllerian Hormone (AMH) Level: AMH is a hormone produced by developing follicles in the ovaries. A lower AMH level is associated with diminished ovarian reserve and may indicate an increased risk of poor ovarian response.
  • Age: Advanced maternal age is a well-established risk factor for poor ovarian response. Women over the age of 35 or 40 are more likely to experience diminished ovarian reserve and reduced response to ovarian stimulation.
  • Previous Ovarian Stimulation Cycles: Patients who have undergone previous IVF cycles and experienced poor ovarian response may be at a higher risk of poor response in subsequent cycles.

What are the typical treatment options available for poor responders in IVF?

For poor responders in IVF, we may employ various treatment strategies aimed at optimizing ovarian response and improving the chances of success. Some typical treatment options include:

  • Adjusted Ovarian Stimulation Protocols: we may modify the standard ovarian stimulation protocol to tailor it to the individual needs of poor responders. This may involve adjusting the type, dosage, or timing of fertility medications used for ovarian stimulation. For example, using a high-dose gonadotropin protocol or a long agonist protocol may be considered.
  • Addition of Adjuvant Medications: Certain adjuvant medications or supplements may be added to the ovarian stimulation protocol to enhance ovarian response. For example, growth hormone supplementation has been shown to improve follicular development and response to ovarian stimulation in some poor responders.
  • Gonadotropin Releasing Hormone (GnRH) Agonist Priming: GnRH agonist priming involves the administration of a GnRH agonist in the luteal phase preceding ovarian stimulation. This approach may improve follicular recruitment and synchronization, potentially enhancing ovarian response in poor responders.
  • Natural Cycle IVF: In some cases, natural cycle IVF may be considered as an alternative to conventional ovarian stimulation protocols. This approach involves monitoring the natural menstrual cycle and retrieving the one dominant follicle that develops without the use of fertility medications. While the success rates of natural cycle IVF may be lower than conventional IVF, it may be a suitable option for certain poor responders who do not respond well to ovarian stimulation.
  • Mild Ovarian Stimulation Protocols: Mild ovarian stimulation protocols aim to achieve a more gentle and less aggressive approach to ovarian stimulation. This may involve using lower doses of fertility medications or shorter duration of stimulation to reduce the risk of over-suppression and optimize ovarian response in poor responders.
  • Duo-stimm Stimulation: it involves two stimulations in the same cycle, one in the follicular phase and, after several days of resting, another stimulation in the luteal phase.
  • Embryo Banking: In cases where the number of eggs retrieved is limited, clinicians may recommend embryo banking or multiple cycles of egg retrieval to accumulate embryos for future transfer attempts. This approach allows for the accumulation of embryos over multiple cycles to increase the chances of a successful pregnancy.

It’s important to note that the selection of treatment options for poor responders should be individualized based on a thorough assessment of each patient’s medical history, ovarian reserve, and previous treatment outcomes. Additionally, counseling and support should be provided to help patients navigate the challenges associated with poor ovarian response and make informed decisions about their treatment options.

How do the treatment approaches differ for poor responders compared to standard IVF protocols?

The treatment approaches for poor responders in IVF often differ from standard IVF protocols in several key ways, primarily aimed at optimizing ovarian response and improving the chances of success. The approaches typically differ in the ovarian stimulation protocols: in poor responders we usually use higher doses of gonadotropins, longer duration, and different types of gonadotropins, as well as adjuvant medications, and the different protocols as I have already referred to.

Are there any lifestyle changes or supplements that might improve outcomes for poor responders?

While lifestyle changes and supplements cannot guarantee improved outcomes for poor responders in IVF, some interventions may help optimize overall health and potentially enhance ovarian function. It’s important to note that individual responses may vary, and it’s always best to consult with a healthcare provider before making any significant changes. Here are some lifestyle changes and supplements that may be considered:

  • Maintaining a Healthy Weight: Obesity and being underweight can both negatively impact fertility. Maintaining a healthy weight through balanced nutrition and regular exercise may support overall reproductive health.
  • Stop Smoking: Smoking has been linked to decreased fertility and may adversely affect ovarian function. Quitting can improve overall health and may positively impact fertility outcomes.
  • Limiting Alcohol and Caffeine consumption: Excessive alcohol intake and high caffeine consumption have been associated with reduced fertility. Moderating alcohol and caffeine intake may support reproductive health.
  • Stress Reduction Techniques: High levels of stress can affect hormonal balance and potentially impact fertility. Engaging in stress-reduction techniques such as mindfulness, yoga, meditation, or counseling may be beneficial.
  • Adequate Sleep: Getting enough quality sleep is essential for overall health and may support reproductive function. Aim for 7-9 hours of sleep per night to promote hormonal balance and optimal fertility.
  • Fertility-Friendly Diet: Consuming a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats may support reproductive health. Some evidence suggests that certain nutrients such as antioxidants, omega-3 fatty acids, and folate may have beneficial effects on fertility.
  • Supplements: While supplements should not replace a healthy diet, some may be beneficial for poor responders. These include:
    • Coenzyme Q10 (CoQ10): CoQ10 is an antioxidant that may help improve egg quality and mitochondrial function.
    • DHEA (Dehydroepiandrosterone): DHEA supplementation has been proposed to improve ovarian function and response to fertility treatments in some women with diminished ovarian reserve.
    • Myo-inositol: Myo-inositol supplementation may help improve ovarian function and response to ovarian stimulation in women with polycystic ovary syndrome (PCOS).
  • Acupuncture: Some studies suggest that acupuncture may help improve fertility outcomes by reducing stress, improving blood flow to the reproductive organs, and balancing hormones. It may be considered as a complementary therapy alongside IVF treatment.

It’s important to discuss any lifestyle changes or supplements with a healthcare provider, particularly in the context of infertility treatment. While these interventions may support overall health and well-being, they may not necessarily lead to improved fertility outcomes for every individual. Additionally, it’s essential to address any underlying medical conditions and follow personalized treatment recommendations provided by fertility specialists.

What are the success rates for IVF treatment among poor responders compared to other patients?

Success rates for IVF treatment among poor responders can vary widely depending on various factors, including the specific characteristics of the patient, the underlying cause of poor ovarian response, and the treatment protocols used. Generally, poor responders tend to have lower success rates compared to patients with a more favorable ovarian response.
While it’s challenging to provide specific success rate estimates for poor responders due to the heterogeneity of this patient population, studies have reported success rates ranging from 5% to 15% per IVF cycle. These success rates may be influenced by factors such as the woman’s age, ovarian reserve, previous treatment history, and the specific protocols used during IVF treatment.

How many cycles of IVF are typically recommended for poor responders before considering alternative options?

The number of cycles of IVF recommended for poor responders before considering alternative options can vary depending on individual circumstances, including factors such as the patient’s age, ovarian reserve, previous treatment history, and response to IVF treatment.
After several failed treatments fertility specialists typically reassess treatment plans and discuss alternative options.

Are there any experimental or emerging treatments specifically aimed at improving outcomes for poor responders?

  • Ovarian Rejuvenation Therapy: with two possibilities:
    • Intraovarian Injection of Autologous Platelet-Rich Plasma (PRP): PRP contains growth factors and cytokines that may stimulate ovarian function and promote follicular development. Intraovarian injection of autologous PRP has been investigated as a potential treatment for poor ovarian response, with some studies reporting improvements in ovarian reserve and response to stimulation.
    • Ovarian Stem Cell Transplantation: Ovarian stem cell transplantation involves the transplantation of stem cells into the ovaries with the aim of replenishing ovarian follicles and improving ovarian function. While still in the experimental stages, this approach holds potential for restoring fertility in women with poor ovarian response.
  • Mitochondrial Transfer: Mitochondrial transfer involves the transfer of mitochondria from donor eggs or cells into the eggs of poor responders with the aim of improving egg quality and developmental potential. This approach may help overcome mitochondrial dysfunction, which is associated with poor ovarian response and age-related infertility.
  • In Vitro Activation (IVA) of Ovarian Follicles: In vitro activation (IVA) involves the removal and activation of dormant follicles from the ovaries, followed by in vitro maturation and fertilization of the retrieved eggs. This approach may offer a potential treatment option for women with primary ovarian insufficiency or poor ovarian response.

What are the risks and potential complications associated with IVF treatment for poor responders?

The risks and potential complications are the same for all IVF treatments and may vary depending on individual patient factors, treatment protocols and medical history. While IVF is generally considered safe, it’s important for patients to be aware of the potential risks and discuss them with their healthcare providers. Some of the risks and potential complications associated with IVF treatment for poor responders include:

  • Ovarian Hyperstimulation Syndrome (OHSS): It is a potential complication of ovarian stimulation medications used in IVF treatment. Poor responders may be at a lower risk of developing severe OHSS due to the lower number of follicles produced, but it can still occur in some cases, particularly if higher doses of gonadotropins are used.
  • Multiple Pregnancy: IVF treatment increases the risk of multiple pregnancies, including twins, triplets, or higher-order multiples. Poor responders may be at a lower risk of multiple pregnancy due to the lower number of embryos transferred, but it’s still a consideration, particularly if more than one embryo is transferred to compensate for lower success rates.
  • Ectopic Pregnancy: IVF treatment is associated with a slightly higher risk of ectopic pregnancy, where the embryo implants outside the uterus, typically in the fallopian tubes. Poor responders may have a lower overall pregnancy rate, but the risk of ectopic pregnancy still exists, especially if tubal factors are present.
  • Ovarian Torsion: Ovarian torsion, where the ovary twists on its blood supply, is a rare but potential complication of IVF treatment. Poor responders may have a lower risk of ovarian torsion due to the smaller number of follicles produced, but it’s still a consideration, particularly during ovarian stimulation.
  • Emotional and Psychological Stress: IVF treatment can be emotionally and psychologically stressful, especially for patients undergoing multiple cycles without success. Poor responders may face additional emotional challenges due to lower success rates and the uncertainty of treatment outcomes.
  • Financial Burden: IVF treatment can be expensive, and poor responders may require multiple cycles to achieve a successful outcome. The financial burden of repeated treatment cycles can be significant and may impact patients’ emotional well-being and quality of life.
  • Treatment Failure and Disappointment: Despite adjustments to treatment protocols, some poor responders may not achieve a successful pregnancy with IVF treatment. Treatment failure can be emotionally challenging and may lead to feelings of disappointment, grief, and uncertainty about future fertility options.
  • Rare Complications: While rare, IVF treatment carries a small risk of rare complications such as ovarian abscess, ovarian cyst rupture, or adverse reactions to fertility medications. These complications may occur in any patient undergoing IVF treatment, including poor responders.

How does age impact the response to IVF treatment among poor responders?

Age significantly impacts the response to IVF treatment among poor responders, as it does for all patients undergoing fertility treatments. Advanced maternal age is associated with:

  • reduced ovarian reserve, which results in a decreased ovarian response
  • decreased egg quality, characterized by chromosomal abnormalities, and decreased development potential. Poor responders who are older may have eggs of lower quality, which can affect embryo quality, implantation potential, decrease in pregnancy rates, and increase in miscarriage rates.

Are there any specific criteria or benchmarks used to determine when to stop attempting IVF treatment for poor responders?

Deciding when to stop attempting IVF treatment for poor responders is a complex and individualized decision that depends on various factors, including the patient’s medical history, age, ovarian reserve, response to treatment (previous IVF cycles), emotional well-being, financial considerations and personal preferences.

While there are no strict criteria or benchmarks universally used to determine when to stop IVF treatment for poor responders, several considerations, as the above stated, may guide this decision-making process.

We should give patients all the information we possess and help them make a decision. Usually, after 3 cycles without achieving a pregnancy with few embryos of bad quality, we suggest exploring alternative fertility treatments. Also, when the woman’s age is over 42, due to lower pregnancy rates with their own eggs, success chances are lower than 5%.

What alternative fertility treatments or options exist for poor responders who do not have success with IVF?

If multiple IVF cycles have been unsuccessful, fertility specialists may explore alternative fertility treatments or pathways to parenthood with patients, such as donor egg IVF, embryo donation, adoption, or child-free living. These alternative options may offer patients alternate pathways to building their families if IVF treatment is not successful.

How does the cost of IVF treatment for poor responders compare to standard IVF treatment?

The cost of IVF treatment for poor responders can vary depending on several factors, including the specific treatment protocols used, the number of cycles required, any additional testing or procedures needed, and the individual patient’s medical history and needs.
In general, the cost of IVF treatment for poor responders may be comparable to or slightly higher than standard IVF treatment due to the additional challenges and complexities associated with poor ovarian response. Here are some factors that make the cost of IVF in low responders higher than in normal responders:

  • They may require multiple IVF cycles to achieve a successful outcome,
  • They may require specialized treatment protocols, medications, or adjunctive therapies to optimize ovarian response and improve treatment outcomes. These additional interventions may incur higher costs compared to standard IVF treatment.
  • Some poor responders may benefit from advanced laboratory techniques, such as preimplantation genetic testing (PGT) or time-lapse imaging, to improve embryo selection and increase the chances of successful implantation.
  • They may receive adjunctive therapies or supplements to enhance ovarian response and improve treatment outcomes. These therapies may include growth hormone supplementation, androgen pretreatment, or intraovarian injection of PRP, which may add to the overall cost of treatment.

Can you discuss any ongoing research or clinical trials focused on improving IVF outcomes for poor responders?

Ongoing research and clinical trials are actively exploring various approaches to improve IVF outcomes for poor responders. While research in this area is continually evolving, some current areas of focus include:

  • Ovarian Rejuvenation Therapies: Research is investigating the potential of ovarian rejuvenation therapies, such as platelet-rich plasma (PRP) injections, stem cell therapies, and growth factor treatments, to improve ovarian function and response to ovarian stimulation in poor responders. Clinical trials are evaluating the safety and efficacy of these therapies in enhancing fertility outcomes.
  • Oocyte and Embryo Quality Assessment: Research is focusing on developing non-invasive methods for assessing oocyte and embryo quality, such as time-lapse imaging, metabolomic profiling, and morphokinetic analysis. These technologies may help identify viable embryos with the highest implantation potential, thereby improving pregnancy rates in poor responders.
  • Genetic and Molecular Biomarkers: Studies are exploring genetic and molecular biomarkers associated with poor ovarian response to identify predictive markers of ovarian reserve and treatment response. By better understanding the underlying mechanisms of poor ovarian response, researchers aim to develop targeted interventions and personalized treatment approaches for this patient population.
  • Reproductive Immunology: Research in reproductive immunology is investigating the role of immune factors and cytokines in ovarian function and response to ovarian stimulation. Clinical trials are exploring immunomodulatory therapies and cytokine-based treatments aimed at improving ovarian response and IVF outcomes in poor responders.

These are just a few examples of the ongoing research and clinical trials focused on improving IVF outcomes for poor responders. As our understanding of the underlying mechanisms of poor ovarian response continues to evolve, it is hoped that these advancements will lead to more effective treatments and better outcomes for patients facing fertility challenges.

Are there any specific support resources or counseling services available for individuals who are struggling with IVF treatment as poor responders?

  • Fertility Clinics and Support Groups: Many fertility clinics offer support groups, counseling services, and educational resources for patients undergoing infertility treatment, including those experiencing challenges as poor responders. These support groups provide a safe space for patients to share their experiences, ask questions, and receive support from others who understand what they are going through. They may also have mental health professionals experienced in infertility and reproductive health to help those patients who need it.
  • Online Forums and Communities: There are numerous online forums, message boards, and social media groups dedicated to infertility and IVF support. These online communities allow individuals to connect with others facing similar challenges, share advice and encouragement, and access valuable resources and information.
  • Mind-Body Programs: Mind-body programs, such as yoga, meditation, acupuncture, and relaxation techniques, can help individuals manage stress, reduce anxiety, and promote overall well-being during infertility treatment. These complementary approaches can complement medical treatment and support emotional and physical health.
  • Financial Assistance and Support Programs: Financial concerns are often a significant source of stress for individuals undergoing IVF treatment. Some fertility clinics offer financial assistance programs, grants, and discounted services to help alleviate the financial burden of infertility treatment.

What are the emotional and psychological aspects that poor responders often face during IVF treatment, and how do you address them?

Poor responders undergoing IVF treatment often face a range of emotional and psychological challenges that can significantly impact their well-being and quality of life. These challenges may include feelings of disappointment and frustration, anxiety and stress, grief and loss, isolation and social withdrawal, pressure and self-blame, adding also the possible financial strain.

Can you provide examples of successful cases where individuals classified as poor responders achieved pregnancy through IVF, and what factors contributed to their success?

As IVF treatments for poor responders need to be adapted to each case, depending on the many factors I have mentioned in the previous questions, the answer to this last question is that we have had successful cases with patients classified as poor responders, which is why we continue to treat them and encourage them.

However, the contributing factors for their success have been a combination of the different techniques and recommendations that I have previously mentioned. There is no easy answer nor a specific single factor. Each case needs to be carefully assessed and the specialists treating the patients need to discuss with them the several strategies and adopt the ones they consider will work best for each poor responder.