Female fertility part two: how to improve fertility
Global trends, a protocol for improving fertility and what the future holds.
Intro
If you want to learn more about how female fertility works and why you should consider freezing your eggs, read part one of this series here. In part two, I will share data on global fertility trends, a protocol for improving fertility, and some of the most promising tech-enabled advancements that will reshape reproductive health.
Why fertility is declining
The global total fertility rate has decreased from about 4.8 children per woman in 1950 to 2.2 in 2021. Projections indicate it will continue to decline, reaching about 1.6 by 2100. This decline can be attributed to several factors:
Education and female empowerment: As women gain access to better education and career opportunities, they tend to have fewer children. Higher educational attainment for women is strongly correlated with lower fertility rates.
Economic development: As countries become wealthier and more developed, birth rates tend to decrease. Children are no longer seen as economic assets for agricultural labor, and the costs of raising children in developed economies are higher.
Declining infant mortality: With better healthcare, fewer children die in infancy, reducing the need for families to have many children to ensure some survive.
Changing social norms: In many societies, there's less pressure to have large families, and people are choosing to have fewer children or remain childless. Many people are also choosing to have children later in life, often resulting in smaller family sizes.
Environmental factors: Research suggest that pollution and environmental toxins may be affecting fertility rates, though the precise mechanisms are not yet fully understood.
As for infertility, approximately 17.5% of the adult population worldwide, or roughly 1 in 6 people, experience infertility. This translates to about 186 million individuals globally. It's challenging to make direct comparisons with rates from 100 years ago due to limited historical data and differences in diagnostic criteria. However, some variables suggest that infertility rates may have increased:
Improved diagnosis: Better medical technology and awareness have led to increased diagnosis of infertility cases that might have gone undetected in the past.
Delayed childbearing: More people are choosing to have children later in life, which can impact fertility.
Lifestyle changes: Factors like obesity, smoking, and stress contribute to infertility.
Environmental factors: Exposure to certain chemicals and pollutants may affect reproductive health.
Male infertility: There's evidence of a decline in sperm quality and quantity over the past several decades, which may contribute to higher infertility rates.
Infertility affects both men and women, and its causes can be attributed to either partner or remain unexplained. Here’s a general breakdown of the proportions:
Female factors: Approximately 30-40% of infertility cases are due to female factors such as ovulation disorders, fallopian tube damage, endometriosis, and uterine or cervical problems.
Male factors: About 30-40% of infertility cases are due to male factors including low sperm count, poor sperm motility, abnormal sperm morphology, and issues with sperm delivery.
Combined factors: In 10-20% of cases, both partners have identifiable issues contributing to infertility.
Unexplained infertility: In about 10-20% of cases, no specific cause can be identified despite thorough testing of both partners. This is known as unexplained infertility.
How to improve fertility
Women can't change the number of eggs they have (other than preserving as many as possible early through egg freezing). However, there are several ways to improve the quality of your eggs and enhance fertility. This applies whether you are trying to conceive naturally or preparing for egg/embryo freezing and IVF. High-quality eggs and sperm increase the chances of successful fertilization, embryo development, and implantation during IVF. Similarly, improving sperm quality can significantly boost fertility. Here are ten evidence-supported ways to improve your fertility:
1. Do not ignore your age
Age is still the number one predictor of success when it comes to pregnancy and fertility treatments. This is not to create pressure or fear, but if you want to have kids at some point in the future—or even if you’re not sure yet—it helps to do the math and hedge your bets by taking action or preventative measures sooner. As a reminder, at age 40, your chance of pregnancy per month is about 5%. At age 30, it’s 20%
2. Stop smoking cigarettes and marijuana.
Smoking accelerates the loss of eggs and reduces their quality, leading to a higher rate of chromosomal abnormalities. Chemicals in cigarettes, such as nicotine and carbon monoxide, can harm ovarian function, leading to reduced estrogen production and irregular menstrual cycles. Smoking can also damage the fallopian tubes, increasing the risk of ectopic pregnancies and preventing the egg from traveling properly. In men, smoking can reduce sperm count, motility, and morphology.
THC, the active component in marijuana, can disrupt the hypothalamus-pituitary-gonadal axis, leading to hormonal imbalances that affect ovulation. Chronic marijuana use may negatively impact egg quality, similar to smoking. In men, marijuana use can reduce sperm count and motility and increase abnormal sperm morphology.
3. Monitor your menstrual cycle
If you notice changes in your menstrual cycle - skipped periods, periods that are irregular (one month you get a period at 25 days, the next month at 34 days and so on), or periods that are closer together (you used to get a period every 29 days and now it comes every 24 days), go see a doctor. Ask for an AMH test and if you have other symptoms, discuss the appropriate tests to rule out conditions that could affect your fertility.
On the other hand, having regular periods doesn't necessarily guarantee perfect fertility. Here’s why:
Anovulation: It's possible to have regular menstrual cycles without ovulating. You may experience anovulatory cycles, where an egg is not released, even though you have regular bleeding.
Poor egg quality: As you age, egg quality declines, which can impact fertility even if periods remain regular. This becomes more pronounced after age 35.
Uterine abnormalities: Conditions like fibroids, polyps, endometriosis, or an irregularly shaped uterus can interfere with implantation despite regular cycles.
Luteal phase deficiency: Sometimes, the second half of the menstrual cycle (luteal phase) may not produce enough progesterone to support a pregnancy, despite having regular cycles.
Hormonal imbalances: You can have regular periods but still have hormonal imbalances that can affect fertility, such as thyroid issues, elevated prolactin levels, or polycystic ovary syndrome (PCOS).
4. Prevent sexually-transmitted diseases
Chlamydia, in particular, can have severe and lasting effects on fertility if left untreated. It can spread to the uterus, fallopian tubes, and ovaries, leading to Pelvic Inflammatory Disease (PID). PID can cause inflammation, scarring, and blockages in the fallopian tubes, which can prevent the egg from traveling to the uterus, leading to infertility or an increased risk of ectopic pregnancy.
5. Start preparing your body in advance
In general, both partners should start preparing their bodies at least 3 months (ideally longer) in advance of trying to conceive or before an egg freezing cycle. This allows enough time to get nutritional stores optimized, get any health issues addressed, and make lifestyle adjustments to boost fertility.
If you’ve been on birth control for years, it’s best to give your body extra time to adjust, as it can often take up to six months for your menstrual cycle to regulate. During this time, you might discover hormonal imbalances that had been there all along, masked by the hormonal birth control.
Early preparation can improve egg quality which increases the chances of a healthy pregnancy. In addition to the recommendations outlined above, you should discuss with your doctor about taking supplements that have been shown to support egg quality and fertility:
Folic acid
Vitamin D
Ubiquinol
Omega-3 Fatty Acids
Iron
Zinc
Inositol (particularly beneficial for women with PCOS)
A quality prenatal with appropriate levels of key nutrients and the right type of B-vitamins (methylated if you have the MTHFR genetic variations)
For men, it takes around 64-74 days or 2-3 months to generate a new, complete pool of mature, healthy sperm capable of fertilizing an egg effectively. This gives you the opportunity to make lifestyle changes (quit smoking, limit alcohol, maintain a healthy weight, avoid excessive heat exposure to the testicles) and supplement to maximize sperm quality. Men can also take a number of supplements including zinc, folic acid, vitamin C, Ubiquinol, vitamin E, Omega-3 and selenium.
6. Limit exposure to plastics and other environmental toxins
BPA is a chemical found in many plastics that can mimic estrogen in the body, disrupting the endocrine system and leading to hormonal imbalances. This can affect both ovarian function and menstrual cycles in women. Exposure to BPA has been linked to reduced egg quality and lower fertilization rates. In men, BPA exposure can decrease sperm count, motility, and quality.
Pesticides, heavy metals (lead, mercury), and air pollutants act as endocrine disruptors, while also raising levels of inflammation and inducing oxidative stress, which can damage DNA in eggs and sperm.
Avoid drinking and eating from plastic, drink clean, filtered water, use air purifiers and test toxicity with blood tests.
7. Eliminate processed foods
Processed foods contain additives, preservatives, and artificial ingredients that can disrupt the endocrine system and hormonal balance, essential for reproductive health. Processed foods also have low levels of antioxidants, which are essential for protecting eggs and sperm from oxidative damage. The high sugar content in processed foods can lead to insulin resistance, which is associated with conditions like polycystic ovary syndrome (PCOS) and can also lead to weight gain which further impact fertility. Processed meats, in particular, have a negative impact on male reproductive health, including semen quality and sperm count, as well as IVF outcomes.
Instead, eat a whole-food, anti-inflammatory diet that is rich in vegetables, healthy fats, protein and fruit. Research consistently points to a Mediterranean-style diet rich in unsaturated fats, whole grains, legumes, fruits, vegetables, and a variety of protein sources as beneficial for fertility. Healthy fats including fatty fish, olive oil, nuts and seeds and full-fat dairy are very important in supporting hormone health. You also need adequate amounts of unrefined carbohydrates and protein for cellular function and hormone balance.
8. Maintain a healthy weight
Being obese or underweight can negatively impact fertility in both women and men by disrupting a number of reproductive functions.
Fat cells produce estrogen, and excessive body fat can lead to an overproduction of estrogen, disrupting the hormonal balance necessary for ovulation and regular menstrual cycles. Excess weight can cause irregular menstrual cycles and anovulation (lack of ovulation), making it difficult to predict fertile windows and reducing the chances of conception.
Overweight and obese women are at higher risk for insulin resistance, which can interfere with ovulation and is associated with conditions like polycystic ovary syndrome (PCOS), a common cause of infertility.
Overweight and obese women also have a higher risk of miscarriage or pregnancy complications.
Conversely, insufficient body fat can lead to low estrogen levels, disrupting menstrual cycles and leading to anovulation. Severe underweight or excessive exercise can cause the hypothalamus to stop releasing hormones that regulate the menstrual cycle, leading to amenorrhea (absence of menstruation).
Nutrient deficiencies common in underweight women can impair egg quality and reduce the likelihood of successful conception and pregnancy.
In men, being both overweight and underweight can impact testosterone levels as well as reduced sperm count and motility.
9. Do not ignore lifestyle factors
Sleep and exercise can be overlooked, but they are vital for fertility because they help regulate key physiological processes that influence reproductive health.
Adequate sleep ensures the proper functioning of the endocrine system, which governs hormone production and balance, including those critical for ovulation and sperm production. Poor sleep can lead to hormonal imbalances, increasing stress levels and disrupting menstrual cycles. Regular exercise improves blood circulation, enhances the delivery of oxygen and nutrients to reproductive organs, and helps maintain a healthy weight, all of which are crucial for optimal fertility.
10. Have sex at the right time
If anyone needs reminding, the most fertile period for conception is the five-day window ending on the day of ovulation, with the highest probability of conception occurring on the day of ovulation itself. This window is critical because the released egg can only be fertilized within 12-24 hours after ovulation, and sperm can survive in the woman’s body for up to 5 days. Having sex every day or every other day during the fertile window can increase the chances of pregnancy.
If you are looking for more resources on how to improve fertility, I recommend this book that provides in-depth guidance on improving egg quality when looking to conceive or freeze eggs. Dr. Natalie Crawford is also a great resource for everything fertility-related and has an entire podcast dedicated to the topic.
The future of fertility
Innovation in the reproductive health space will bring forth remarkable disruption in the coming decades. Already, several companies are making significant advancements in areas such as AI, robotics, and stem cell research. These new technologies will make fertility treatments more effective, accessible, and personalized, potentially increasing success rates while reducing the emotional and financial burdens on patients. Below, I briefly highlight some of the most promising areas of innovation.
1. Advanced Reproductive Techniques
In Vitro Gametogenesis (IVG): Researchers are making progress on techniques to create viable eggs and sperm from a patient's ordinary somatic cells (any cell taken from the body), through cellular reprogramming into stem cells and then gametogenesis. IVG could provide an unlimited supply of gametes (reproductive cells), overcoming age-related infertility and allowing same-sex couples to have genetically-related children. Clinical trials for human IVG are still a few years away, but IVG could be available within 5-10 years if trials are successful.
Ovarian tissue cryopreservation (OTC) is an emerging and promising technique that involves the removal, freezing, and later re-implantation of ovarian tissue. The primary purpose of this procedure is to preserve fertility for women who may lose their ovarian function due to medical treatments, such as chemotherapy or radiation therapy, or due to certain medical conditions.
2. Genetic Screening and Editing
Preimplantation Genetic Testing (PGT): Advanced genetic screening like preimplantation genetic testing (PGT) is increasing the ability to select viable embryos. PGT for embryo screening is already widely available. Combining this with AI analysis of time-lapse embryo imaging could further optimize embryo selection for transfer.
CRISPR and Gene Editing: CRISPR technology has the potential to edit genes in embryos to eliminate genetic disorders and enhance the viability and health of embryos resulting from IVF. Despite its revolutionary potential, CRISPR technology still faces technical, regulatory, and ethical challenges.
3. Regenerative Medicine
Stem Cell Therapy: Research is ongoing into using stem cells to repair or replace damaged reproductive tissues, such as ovarian tissue, potentially restoring fertility in patients with conditions like premature ovarian failure.
Ovarian Rejuvenation: Techniques such as platelet-rich plasma (PRP) therapy are being explored to rejuvenate aging ovaries and improve egg quality and quantity. The primary goal of ovarian rejuvenation is to improve fertility in women who have diminished ovarian reserve and potentially delay menopause.
4. AI and Machine Learning
Predictive Analytics: AI can analyze large datasets to predict the success rates of fertility treatments, personalize treatment plans, and improve patient outcomes. Companies like Future Family, Kindbody, and Carrot Fertility already leverage data analytics to personalize fertility treatments.
Image Analysis: Machine learning algorithms can assess embryo quality more accurately than human embryologists, enhancing the selection process. By selecting embryos with the highest potential for successful implantation and development, AI can improve IVF success rates and reduce the number of cycles needed.
5. Automation and Miniaturization
Microfluidic "lab-on-a-chip" devices could automate and miniaturize the entire IVF process from gamete handling to embryo culture and selection. This could dramatically reduce costs and improve consistency compared to manual IVF labs. Companies like Univfy, Alife Health, Overture Life are using AI, machine learning, and microfluidics to automate and optimize IVF processes. TMRW created the world’s first and only FDA-cleared, automated platform for the safe management of frozen eggs and embryos.
6. Artificial Wombs
Looking even further ahead, ectogenesis or artificial womb technology could allow women without a functional uterus to effectively "give birth" by gestating fertilized eggs in an external womb-like device. This could benefit those with uterine abnormalities or who have undergone hysterectomies. While still highly experimental, some scientists believe rudimentary artificial wombs for human use could potentially emerge in 10-20 years.