POF (Premature Ovarian Failure) and motherhood? Causes, symptoms, diagnosis and treatment options and prognosis.

Halyna Strelko, MD
Co-founder& Leading Reproduction Specialist at IVMED Fertility Center, IVMED

Category:
Low Ovarian Reserve

premature-ovarian-failure-and-motherhood
From this video you will find out:
  • What is Premature Ovarian Failure (POF), and how does it affect a woman’s ability to become a mother?
  • What are the causes and symptoms of POF, and how does it differ from early menopause?
  • What is the role of progesterone and estrogens in a woman’s reproductive health, and how does POF affect the production and balance of these hormones?
  • What is the average age at which women go through menopause?
  • What are the methods used to diagnose POF, and when should women seek diagnosis?
  • What are the available treatment options for POF, and how do they impact a woman’s fertility?
  • What is the difference between POF and POI (Premature Ovarian Insufficiency), and how are they related?
  • How common is POF in the general population?
  • What are the known risk factors for developing POF?

POF (Premature Ovarian Failure) and motherhood? Causes, symptoms, diagnosis and treatment options and prognosis.

Are you seeking answers about Premature Ovarian Failure (POF) and how it might impact your dreams of motherhood? In this session, Dr Halyna Strelko, Co-founder & Leading Reproduction Specialist at IVMED Fertility Center will walk you through available treatment options, diagnosis, and symptoms.

Understanding Premature Ovarian Insufficiency and Premature Menopause

Normally, the ovaries produce estrogens and progesterone, and these hormones have a complex effect on the whole body. All organs and systems react and change with these sex hormones. When the levels of these hormones decrease, the entire body also changes. As it is shown in the diagram, the levels of estrogens start to decrease after 40 years old and progressively decrease if it’s a normal menopause until the age of 60–70 years old.

The effects of estrogens are widespread. Not only are the ovaries and sexual organs involved, but estrogens also protect the heart from the action of cholesterol, liver, and bones. They also protect the brain because when estrogen levels decrease, we can experience some mental issues, such as sleep disturbances, mood changes, and other problems related to brain function. There can also be issues with the uterus and ovaries when the levels of estrogens hormones decrease. Estrogen also can protect against free radicals, meaning that high levels of estrogen protect us from changes due to ageing.

Another important hormone is progesterone. This hormone is involved in the second phase of a menstrual cycle, providing a calming effect on the brain, reducing inflammation, relaxing blood vessels, decreasing blood pressure, assisting liver and kidney health, and retaining bone density. So, there are numerous effects, and when we lose all these protective effects, we can experience various symptoms, including hot flashes, changes in blood pressure, night sweats, insomnia, vaginal dryness, menstrual disorders, weight gain, and fatigue. Not all of these symptoms are present in every woman, but several are typically experienced by women with ovarian insufficiency.

Another important point is that the decrease in estrogen hormones produces a lot of negative emotional influences. About 52% of women with premature ovarian insufficiency experience negative impacts on their emotional state, and 88% report depression. Many also report fatigue, decreased performance, irritability, loss of memory, and energy. It’s important to understand why all these issues appear and how to protect yourself. When people understand the condition, they are more prepared to take action. Often, if a patient doesn’t understand what’s happening, they may see various doctors and struggle to find a solution.

Understanding the causes

As the European Society of Human Reproduction guidelines state, premature ovarian insufficiency refers to the loss of ovarian function before the age of 40 years old. This age is significant because natural menopause typically occurs around 50 years old, plus or minus 4 years. Around 1% of people experience menopause before the age of 40 years old, and 10% experience it between 40 and 50 years old. This means that premature ovarian failure affects a small percentage of the population, and in some cases, it can occur as early as age 30 or even 20. It’s essential to understand the prevalence of this condition and why it’s important to discuss it.

Premature ovarian insufficiency, also known as premature menopause, has various consequences. The deficiency in estrogen and progesterone can lead to general health problems, including accelerated cognitive impairment, cardiovascular diseases, autoimmune diseases, and infertility. It can also impact a woman’s sense of well-being and quality of life, often leading to high emotional stress due to isolation and stigma. The diagnostic process can be challenging, and many women feel guilty about their reproductive issues.

The main etiology of premature ovarian insufficiency can be genetic, autoimmune, oncological treatment-related, or idiopathic. Approximately 50% of cases are idiopathic, meaning that there’s no specific cause identified. Genetic causes account for around 10% of cases and can include conditions like Turner syndrome and Fragile X syndrome. Autoimmune issues are associated with 15-20% of cases. Infections, like those related to sex development or diseases such as HIV, tuberculosis, and malaria, can also contribute. Environmental factors such as smoking, surgery, and radiation therapy may lead to premature ovarian insufficiency.

If there’s no identifiable cause, current guidelines state that there’s no proven predictive test to identify women who will develop premature ovarian insufficiency. Therefore, it’s crucial to educate patients about the modifiable and non-modifiable risk factors and discuss fertility preservation and reproductive plans early on.

Preventive measures and diagnosis

The diagnosis of premature ovarian insufficiency is based on the presence of menstrual disturbances, with oligo-amenorrhea lasting at least four months and an FSH level of more than 25 units per liter on two occasions, with more than four weeks between tests. About 10% of women are diagnosed with ovarian failure between 40 and 50 years old, which increases to 10-15% in populations seeking fertility treatment.

To improve prognosis, lifestyle factors such as quitting smoking, maintaining a healthy diet, and controlling body mass index are crucial. A well-balanced, protein-rich vegetarian diet, physical activity, and regular intake of fruits and vegetables can positively influence ovarian reserve.

There is also a link between body mass index (BMI) and ovarian failure. This link is still unclear. A very low body mass index may provoke earlier ovarian insufficiency, but with a high body mass index, in some publications, it is considered beneficial. We can also say that early menopause is related to some ethnicities, like African and Latin American ethnicities. Low weight and, surprisingly, low IQ are associated with earlier menopause, while the European ethnicity is linked to later menopause. Physical activity, being a little overweight, and having a high socioeconomic status also play a role.

Management and solutions for Premature Ovarian Insufficiency

So, what can we do in this situation? If we meet patients with premature ovarian insufficiency, with high levels of FSH and low levels of AMH, it’s necessary to see if there is some genetic problem. It’s necessary to advise the patient to do karyotype testing because it can help detect conditions like Turner syndrome, which is crucial for understanding potential complications and specific management. Also, it’s important to discuss potential surgical interventions, as ovaries in this case may be more prone to oncological diseases. If we find mutations of the fmr1 gene (fragile X), discussing the situation with a genetic counselor is vital, as there is a risk of health problems and mental retardation in the children of these women. It’s also essential to check for autoimmune issues because endocrinological control may be necessary in such cases.

Hormonal Replacement Therapy and its indications

Once the diagnostic process is complete, the main treatment is to restore the levels of estrogens and progesterone. Hormonal replacement therapy is often prescribed, and there are various types of estrogen available, such as tablets, capsules, and transdermal forms. Progesterone is needed if the woman has a uterus to protect the uterine lining from hyperplasia or cancer. Generally, indications for hormonal replacement therapy include vasomotor symptoms, genitourinary symptoms, issues with sexual life, and overall quality of life.

Monitoring and alternatives to Hormonal Therapy

Monitoring the therapy involves regular check-ups, including ultrasound and mammography. It’s crucial to be aware of the risk of thrombosis, as steroid hormones may have some relation to this risk. Transdermal or vaginal forms are considered less risky than tablets.

Many patients inquire about alternatives to hormonal therapy, such as psychotherapy, homeopathy, relaxation techniques, acupuncture, and herbal medicine. While these methods may alleviate symptoms like sleep disturbances or mood swings, they may not have the same comprehensive effects as hormonal replacement therapy on bone density, cardiovascular health, and sexual function.

Regarding diet and supplements, antioxidants like melatonin, coenzyme Q10, and vitamins C and E can help compensate for the deficiency of estrogen and provide protective effects. The recommended diet includes oily fish, dairy consumption, fruits, and vegetables.

Egg Donation as an option

Finally, if the ovarian reserve is depleted, and no follicles or eggs are detectable, egg donation is a potential option. The specific conditions that indicate egg donation include women with hypergonadotropic hypogonadism, advanced reproductive age, very diminished ovarian reserve, and those with some genetic conditions or poor egg quality. Partners with several unsuccessful treatments may also consider egg donation.

Conclusions

In conclusion, understanding premature ovarian insufficiency is essential as it can significantly impact a woman’s health and well-being. Proper diagnosis, treatment, and lifestyle choices can help mitigate the effects of this condition and improve a patient’s quality of life.

- Questions and Answers

My AMH is 3.2, which is very low, and I also have light periods only lasting 2 days. I only had 3 follicles in my last IVF round. Is there anything I can do to increase my follicles? Do you recommend priming or down-regulation for increasing the number of follicles?

Increasing the number of follicles can be challenging. Follicles grow in groups or waves, and it’s important to choose the right moment to start stimulation. Down-regulation may not necessarily improve the situation, but pre-treatments like estrogen or progesterone pre-treatment might help. Coenzyme Q10 and replacement hormonal therapy can also be considered, though they may only result in a slight increase in follicles. The key is selecting the best time to initiate your stimulation.

Can oral contraception impact ovarian receptors for FSH and LH?

Oral contraceptives can impact ovarian receptors for FSH and LH. Prolonged use may reduce LH levels, affecting the ovarian response. The extent of the impact depends on the specific pill and the duration of use. Short-term use may not have significant effects, but long-term use can influence the ovarian response negatively.

Is there a possibility to figure out the ovarian sensitivity to FSH and AMH, or improve it?

Improving ovarian sensitivity to FSH and LH is possible. Growth hormone, luteinizing hormone, and adjusting FSH dosages can enhance ovarian sensitivity. Genetic mutations of FSH and LH receptors may require increased dosages. It’s essential to work closely with your healthcare provider to tailor the treatment to your specific needs.

Are there any other options, in addition to PRP method, to increase the ovarian response? Maybe taking antral follicles and growing them in controlled conditions?

Besides PRP, there is a method called ovarian tissue activation, involving chemical substances to activate ovarian stem cells, which is less common and not widely practised. Conventional methods include using growth hormones and trying different protocols. Egg banking, where you collect and freeze eggs from several cycles, can provide a more reliable option for those with few follicles every cycle. It may be easier and more dependable than experimental methods.

Why do ovaries stop the normal growing process of follicles under stimulation therapy, which aims to stimulate growth? The body reacts the opposite way it should. Are there specific conditions when ovaries stop growing?

Ovarian response can vary based on various factors. Taking oral contraceptives for an extended period can affect LH levels, leading to insufficient stimulation. Mutations in FSH and LH receptors might require adjustments to dosages. Long protocols may involve high suppression of ovarian function, which can reduce LH levels. Modifying natural cycles can be useful for patients with limited ovarian reserves. The choice of the right approach depends on your specific situation.

Is there a fluctuation in FSH, AMH, or TSH levels depending on the day of the blood test?

FSH levels fluctuate during the menstrual cycle, with peak levels around the time of ovulation. The timing of your blood test can influence the FSH result. TSH levels do not fluctuate significantly during the menstrual cycle. However, it’s important to consider the timing of specific tests, such as those for ovarian reserve.

Does artificial testosterone help develop more and better follicles?

There is some conflicting information regarding the use of artificial testosterone in improving follicle development. Some studies suggest that transdermal testosterone or DHEA supplementation may be beneficial, but the results may vary. While it may increase the number of follicles slightly, it is not a guaranteed solution.

When collecting follicles, would you prefer a natural or stimulated cycle?

The choice between a natural or stimulated cycle for collecting follicles depends on the patient’s specific situation. In cases of limited ovarian reserves, a modified natural cycle with some stimulation may be used to optimize the number and quality of the collected oocytes.

Where can I have IVF treatment with no age limit, and what does the situation look like in Ukraine, for example?

Officially, there is no age limit for IVF treatment, but success rates may decrease with advanced maternal age. For using egg or sperm donation, the age of the donor is more critical. The exact situation in Ukraine and other countries may vary, so it’s essential to consult with your healthcare provider for personalized guidance.  
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Authors
Halyna Strelko, MD

Halyna Strelko, MD

Dr Halyna Strelko is the Co-founder & Leading Reproduction Specialist at IVMED Fertility Center, Kiev, Ukraine since 2012. Dr Strelko is a certified member of ESHRE (European Society of Human Reproduction and Embryology) and ASRM (American Society of Reproductive Medicine), UARM (Ukrainian Association of Reproductive Medicine). She had a medical practice in France and medical practice in leading Kyiv’s infertility clinics with over 23 years of experience. She speaks English, French and Italian.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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