Role of vitamin D in reproductive health

Understanding the Crucial Link Between Vitamin D and Fertility

Vitamin D, long celebrated for its role in bone health, is emerging as a pivotal player in reproductive health. From regulating hormonal balance and ovarian function to influencing embryo implantation and pregnancy outcomes, vitamin D’s impact spans across the female reproductive cycle as well as male fertility. This article explores the science behind vitamin D’s role in conception and pregnancy, its potential to enhance assisted reproductive technologies (ART), and the importance of maintaining optimal vitamin D levels for couples striving to conceive.

Vitamin D and Its Biological Role in Reproductive Health

Vitamin D receptors in reproductive tissues

Vitamin D functions biologically through binding to vitamin D receptors (VDRs), which are widely expressed in reproductive tissues for both women and men. In females, these receptors are found in the ovaries, including granulosa and cumulus oophorus cells, the endometrium, and the placenta. In males, VDRs are present in testicular tissue and sperm cells. This distribution allows vitamin D to regulate key reproductive processes such as ovarian follicular development, hormonal synthesis, endometrial receptivity, and immune function necessary for implantation and pregnancy maintenance.

Vitamin D synthesis and sources

The body produces vitamin D3 (cholecalciferol) primarily through skin exposure to ultraviolet B (UVB) sunlight. Vitamin D can also be obtained from dietary sources and supplements, including vitamin D2 (ergocalciferol) and D3. Despite these sources, many individuals—especially women—may experience insufficiency due to limited sun exposure, lifestyle, or physiological factors like higher body mass index or darker skin pigmentation.

Mechanisms of vitamin D action in reproduction

Vitamin D acts by binding to VDRs, triggering gene expression changes that promote hormonal balance and regulation of the hypothalamic-pituitary-gonadal axis. It enhances estrogen production by upregulating aromatase enzyme activity, influencing menstrual cycle regularity and ovulation. Additionally, vitamin D modulates immune responses in reproductive tissues, supporting proper placental implantation and lowering inflammation. These mechanisms collectively contribute to improved fertility and pregnancy outcomes.

What role does vitamin D play biologically in reproductive tissues?

Vitamin D exerts its biological actions through vitamin D receptors (VDRs) present in multiple reproductive tissues in both women and men, including the ovaries, placenta, endometrium, testicular tissue, and sperm. These receptors facilitate vitamin D's regulatory effects on hormonal balance, follicular development, endometrial receptivity, and immune modulation critical for reproductive success.

Impact of Vitamin D on Female Hormonal Balance and Menstrual Function

How does vitamin D influence hormonal balance and menstrual function in women?

Vitamin D plays a vital role in maintaining female hormonal balance and the regularity of menstrual cycles. One of its primary mechanisms is through the regulation of estrogen synthesis. Vitamin D increases the activity of the enzyme aromatase, which converts androgens into estrogens, thereby supporting healthy estrogen levels essential for reproductive function.

Additionally, vitamin D modulates the hypothalamic-pituitary-gonadal (HPG) axis by acting on both the hypothalamus and pituitary gland. This regulation helps control the release of hormones that drive the menstrual cycle and ovulation processes. Consequently, maintaining adequate vitamin D levels contributes to the proper timing and occurrence of ovulation.

Adequate vitamin D status supports normal ovulatory cycles and menstrual regularity, which are critical factors for fertility and reproductive health. Deficiency in vitamin D has been linked to menstrual disorders, including irregular cycles and conditions like polycystic ovary syndrome (PCOS).

Together, these effects demonstrate that vitamin D is integral to the hormonal environment and functional processes underlying the menstrual cycle and ovulation, thereby influencing female fertility outcomes.

Vitamin D Deficiency and Polycystic Ovary Syndrome (PCOS)

What is the relationship between vitamin D deficiency and PCOS?

Vitamin D deficiency is highly prevalent among women with polycystic ovary syndrome (PCOS), affecting between 67% and 85% of cases. This deficiency is not only common but also linked to the severity of PCOS symptoms. Low vitamin D levels contribute to worsened insulin resistance, a core feature of PCOS, and play a role in irregular ovulation and menstrual disturbances often seen in affected women.

How does vitamin D deficiency affect insulin resistance and ovulation in PCOS?

Insulin resistance in PCOS exacerbates hyperandrogenism and disrupts ovulatory function. Vitamin D influences insulin sensitivity by modulating pancreatic β-cell function and systemic inflammation. Deficiency compromises these effects, leading to elevated insulin resistance. Additionally, vitamin D receptors (VDRs) located in ovarian cells suggest a direct role in improving follicular development and ovulation.

What are the benefits of vitamin D supplementation for women with PCOS?

Vitamin D supplementation has demonstrated promising benefits in women with PCOS. Clinical studies reveal that restoring adequate vitamin D levels helps reduce insulin resistance, promotes more regular menstrual cycles, and enhances ovulation rates. Supplementation dosages in research commonly range from 1,000 to 10,000 IU daily for 30 to 60 days, proving safe and effective. These improvements contribute to better reproductive outcomes and may assist in managing PCOS-related infertility.

In summary, addressing vitamin D deficiency in PCOS patients is a valuable adjunct in managing both metabolic and reproductive aspects of the syndrome, paving the way for improved fertility and overall health.

Vitamin D Status and Assisted Reproductive Technologies (ART) Outcomes

How does vitamin D status influence the outcomes of assisted reproductive technologies?

Vitamin D plays a significant role in enhancing the outcomes of assisted reproductive technologies (ART), including in-vitro fertilization (IVF). Women with optimal vitamin D levels, particularly serum concentrations above 30 ng/mL, are more likely to achieve higher clinical pregnancy and live birth rates. Studies show that sufficient vitamin D status is associated with a clinical pregnancy rate of 42.2%, compared to 30.6% in vitamin D-deficient patients undergoing ART.

Vitamin D levels and IVF success

A positive correlation exists between serum vitamin D levels and IVF success. Women with higher serum vitamin D and follicular fluid concentrations tend to have improved pregnancy outcomes after IVF treatments. This association suggests that vitamin D influences the quality of oocytes and the intra-follicular environment, which are critical for successful fertilization and embryo development.

Correlation of follicular fluid vitamin D with pregnancy

The concentration of vitamin D in follicular fluid, the microenvironment surrounding the oocyte, is an important predictor of IVF success. Higher vitamin D levels in this fluid correlate with increased likelihood of achieving clinical pregnancy, indicating that local vitamin D availability supports optimal ovarian function and embryo viability.

Vitamin D effect on ovarian reserve and endometrial receptivity

Vitamin D sufficiency is linked to improved ovarian reserve markers such as anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). Additionally, vitamin D influences endometrial receptivity by increasing endometrial thickness at the time of human chorionic gonadotropin (HCG) administration, which enhances the chances of successful embryo implantation. These effects collectively contribute to better reproductive potential and ART success.

In summary, maintaining adequate vitamin D levels is essential for improving ART outcomes, from oocyte quality and ovarian reserve to endometrial preparedness and implantation success.

Vitamin D and Early Pregnancy: Placental Function and Immune Modulation

What role does vitamin D play in early pregnancy and placental function?

Vitamin D plays a critical role in early pregnancy through its regulation of placental function and immune modulation. It is actively involved in placental implantation by modulating gene expression, notably regulating transcription of the HOXA10 gene, which is essential for successful embryo implantation. This molecular influence supports the establishment and maintenance of pregnancy.

Vitamin D also affects cytokine production within the placenta, helping to balance pro-inflammatory and anti-inflammatory signals. This cytokine modulation creates an immune environment that fosters tolerance towards the developing embryo, preventing maternal immune rejection, which is vital during early gestation.

Moreover, vitamin D receptors (VDRs) are expressed in placental tissue, highlighting the hormone's direct involvement in placental physiology. Through these receptors, vitamin D controls immune responses at the maternal-fetal interface, promoting immune tolerance and protecting against infections that could jeopardize pregnancy.

Collectively, these actions of vitamin D contribute to a favorable immune environment that supports early pregnancy maintenance and placental health. Deficiency in vitamin D has been linked with increased risk of adverse pregnancy outcomes, emphasizing the significance of maintaining adequate vitamin D levels for reproductive success.

Risks of Vitamin D Deficiency During Pregnancy and Maternal-Fetal Health

What pregnancy complications are associated with vitamin D deficiency?

Vitamin D deficiency during pregnancy significantly raises the risk of several serious complications. Among these are preeclampsia—a condition characterized by high blood pressure and potential organ damage—gestational diabetes, and preterm birth. Each of these complications can adversely affect both the mother's and baby's health.

How does vitamin D deficiency impact fetal development?

Low vitamin D levels are also correlated with fetal growth issues, including intrauterine growth restriction (IUGR), where the baby does not grow at a normal rate inside the womb. Moreover, deficient vitamin D during pregnancy has been associated with increased risks for long-term developmental concerns such as autism spectrum disorder and metabolic syndromes in children.

Why is maintaining adequate vitamin D important during pregnancy?

Adequate vitamin D supports proper placental function—regulating implantation, cytokine production, and immune responses crucial in early pregnancy—which helps in reducing oxidative stress and inflammation. Maintaining vitamin D levels above 20-40 ng/mL is advised for minimizing risks and promoting healthy maternal and fetal outcomes.

Ensuring vitamin D sufficiency through supplementation is shown to reduce risks of gestational diabetes, preeclampsia, preterm birth, and other complications, making it a vital consideration for prenatal care.

Benefits and Safety of Vitamin D Supplementation During Pregnancy

Dose recommendations and safety profiles

Vitamin D supplementation during pregnancy is generally considered safe when taken within recommended doses. Most studies endorse daily supplementation in the range of 2,000 to 4,000 IU of vitamin D3. This dose effectively raises and maintains adequate serum vitamin D levels in both mother and fetus without observed adverse effects. Additionally, moderate daily doses between 1,000 to 10,000 IU have also shown efficacy for reproductive outcomes in other female fertility contexts, indicating a broad safety margin for use in pregnancy.

Reduction of pregnancy-related complications through supplementation

Maintaining optimal vitamin D status during pregnancy significantly lowers the risk of multiple complications. Supplementation has been associated with decreased incidence of gestational diabetes, preeclampsia, postpartum hemorrhage, and infections such as bacterial vaginosis. Furthermore, vitamin D sufficiency reduces the likelihood of preterm birth and low birth weight infants, contributing to healthier pregnancy outcomes. These benefits are thought to arise from vitamin D's role in immune modulation, placental function, and hormonal regulation.

Improvement of maternal bone health

Pregnancy naturally increases demands on maternal bone stores, sometimes causing reversible bone loss. Vitamin D supplementation supports improved maternal bone mineral density during pregnancy, helping to prevent this loss and promoting long-term skeletal health for the mother. Ensuring adequate vitamin D intake is critical for calcium and phosphorus balance, essential for bone mineralization throughout gestation.

Vitamin D's low cost and excellent safety profile make it an accessible adjunct therapy for pregnant women to optimize health outcomes for themselves and their babies. Clinicians are encouraged to monitor vitamin D status and recommend supplementation to reduce deficiency risks and support a healthy pregnancy.

Vitamin D and Male Reproductive Health

How does vitamin D affect male fertility and reproductive health?

Vitamin D plays an important role in male reproductive health primarily through its effect on testosterone levels. Adequate vitamin D promotes testosterone production, which is crucial for maintaining libido and erectile function. Men with normal vitamin D levels tend to experience better sexual health and function compared to those who are deficient.

Influence on testosterone levels and sperm quality

Testosterone directly influences male fertility, and vitamin D helps regulate this hormone. Moreover, vitamin D receptors are present in testicular tissue and sperm cells, highlighting vitamin D's role in sperm development and function. Research shows that men with low vitamin D levels often demonstrate reduced sperm motility, which impairs sperm’s ability to reach and fertilize an egg. In addition to motility, deficiencies can lead to lower sperm count and abnormal sperm morphology, further reducing fertility potential.

Effects on libido and erectile function

Vitamin D’s influence on testosterone also contributes to sexual desire and the ability to maintain erections. Men deficient in vitamin D commonly report decreased libido and may experience erectile dysfunction. Optimal levels support sexual health by sustaining hormonal balance and promoting vascular function necessary for erection.

Association with semen parameters

Studies consistently associate vitamin D deficiency with poorer semen quality markers, including motility, count, and morphology. Improved vitamin D status correlates with better semen parameters and increased chances of conception. Animal studies have also shown that vitamin D deficiency can lead to incomplete spermatogenesis and damage in sperm-producing tissues.

Maintaining adequate vitamin D levels through sunlight exposure, diet, and supplementation when necessary is a recommended approach to support male reproductive health and fertility outcomes.

Epidemiology of Vitamin D Deficiency and Its Implications for Reproductive Health

What is the prevalence of vitamin D deficiency among individuals of reproductive age, and what factors influence it?

Vitamin D deficiency is a widespread concern affecting reproductive-aged individuals globally. Approximately 40% of the U.S. population is deficient in vitamin D, with even higher rates among women attending fertility clinics. For instance, studies reveal suboptimal vitamin D levels in nearly 40% of women undergoing fertility evaluations, where 8.8% were classified as deficient (<30 nmol/L) and 31.1% as insufficient (30–50 nmol/L).

Several factors influence these deficiency rates. Seasonal variation plays a significant role, with vitamin D levels dropping markedly in winter months due to reduced sunlight exposure — mean levels can fall from about 72.1 nmol/L in summer to approximately 45.3 nmol/L in winter. Socioeconomic disparities also impact status; state-funded patients show a higher prevalence of suboptimal vitamin D (50.2%) compared to self-funded patients (35.9%). Additionally, factors such as skin pigmentation, overweight status, and dietary intake contribute to variations in vitamin D levels.

Given these influences, routine screening for vitamin D deficiency is particularly vital in women of reproductive age, especially those experiencing infertility or preparing for assisted reproduction. Targeted supplementation is recommended during seasons with low sunlight availability and in socioeconomically vulnerable groups to enhance reproductive health outcomes and reduce risks associated with deficiency during conception and pregnancy.

Vitamin D’s Epigenetic Influence on Fertility and Reproductive Gene Expression

How does vitamin D influence reproductive health through epigenetic mechanisms?

Vitamin D plays a significant role in regulating gene expression through epigenetic mechanisms, which influence reproductive health beyond its hormonal effects. One of the primary ways it does this is by modulating DNA methylation, a process that controls gene activity without changing the DNA sequence itself.

This epigenetic regulation affects key genes involved in reproductive processes. For example, vitamin D modulates the transcription of the HOXA10 gene, which is critical for preparing the endometrium (the lining of the uterus) to be receptive to an embryo. Proper HOXA10 function promotes successful embryo implantation, a necessary step for pregnancy to occur.

By influencing HOXA10 expression via epigenetic modifications such as DNA methylation, vitamin D contributes to endometrial receptivity and thus enhances fertility potential. This demonstrates that vitamin D’s role in fertility involves intricate genetic regulation mechanisms that impact implantation success, complementing its effects on hormonal balance and ovarian function.

Understanding vitamin D's epigenetic roles may open new avenues for improving reproductive outcomes, especially in women facing implantation failures or infertility issues.

Vitamin D Supplementation Protocols to Improve Fertility Outcomes

What supplementation protocols have proven effective for improving fertility outcomes?

Moderate daily doses of vitamin D, ranging from 1,000 to 10,000 IU, administered for 30 to 60 days, have demonstrated safety and effectiveness in infertile women whose serum vitamin D levels are below 30 ng/mL. Such supplementation protocols are associated with significant improvements in clinical pregnancy rates and live birth outcomes.

Research shows that the efficacy of vitamin D supplementation depends on several parameters, including the vitamin D level at baseline, type of vitamin D compound used, total dosage, duration of supplementation, and frequency of administration. Women receiving these moderate daily doses exhibited higher chances of conception and improved reproductive results.

Impact on clinical pregnancy and live birth rates

A systematic review and meta-analysis of 12 studies encompassing over 2,300 infertile women revealed that vitamin D supplementation increased clinical pregnancy likelihood by 70% (odds ratio 1.70, 95% confidence interval 1.24–2.34). This enhancement in fertility outcomes also translated into improved live birth rates, particularly when serum vitamin D levels exceeded 30 ng/mL.

Women undergoing assisted reproductive technologies such as IVF are more likely to conceive and carry a pregnancy to term when vitamin D status is optimized via supplementation. Supplementation was also linked to improved ovarian function, menstrual regularity, and embryo implantation success.

Safety and duration of supplementation

Vitamin D supplementation at moderate doses is considered safe for infertile women. Doses within the 1,000–10,000 IU range do not produce adverse effects and are effective in elevating vitamin D blood levels to optimal thresholds. Duration of supplementation between one to two months is generally sufficient to achieve reproductive benefits.

Ongoing monitoring of vitamin D levels during supplementation is advised to tailor dosing and ensure adequacy without risk of toxicity. Given its favorable safety profile, low cost, and potential reproductive advantages, vitamin D supplementation represents a promising adjunct therapy for women facing fertility challenges.

Couples' Vitamin D Status and Its Influence on Conception Success

Does vitamin D status in both partners affect conception success?

Yes. Research shows that couples in which both partners achieve the recommended vitamin D intake have notably higher chances of conceiving clinical pregnancies. This shared sufficiency translates into improved live birth rates, indicating that the vitamin D status of both individuals contributes synergistically to reproductive success.

Adequate vitamin D levels in men and women positively influence hormonal regulation, sperm quality, and ovarian function. When both partners maintain sufficient vitamin D, this optimizes conditions for fertilization and embryo development, thus decreasing the time to pregnancy.

Studies report that women and their partners who meet estimated average requirements (EAR) for vitamin D intake and possess sufficient serum 25(OH)D levels (≥50 nmol/L) exhibit more than a twofold increase in likelihood to conceive. This underscores the importance of evaluating and managing vitamin D status jointly rather than focusing solely on one partner.

In summary, the combined vitamin D status of couples is a significant factor influencing fertility outcomes, with evidence supporting enhanced conception rates and live births when both partners maintain optimal vitamin D levels.

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Factor	Impact on Fertility	Details
Both partners' vitamin D	Increased conception success	Couples meeting vitamin D EAR show over twice the chance of clinical pregnancy
Time to pregnancy	Shorter duration	Adequate vitamin D intake correlates with faster conception
Live birth rates	Higher outcomes	Sufficient serum 25(OH)D linked with improved live birth frequency
Serum vitamin D threshold	≥50 nmol/L (sufficiency)	Levels associated with maximum fertility benefits in both men and women

Integrating Vitamin D Considerations Into Reproductive Health Services

How do reproductive health services incorporate vitamin D assessment and guidance?

Reproductive health services often include vitamin D screening in their routine fertility assessments. This screening helps identify deficiencies or insufficiencies, which are common in many women seeking fertility care. Once detected, healthcare providers offer tailored counseling on vitamin D supplementation, diet rich in vitamin D, and lifestyle changes such as safe sun exposure practices.

This integrated approach supports optimizing vitamin D levels, which are crucial for hormonal balance, menstrual regulation, and improved ovarian function. Such guidance complements medical interventions like assisted reproductive technologies (ART), potentially increasing the chances of successful conception and healthy pregnancy outcomes.

Lifestyle factors influencing vitamin D

Several lifestyle factors affect vitamin D status. Limited sun exposure due to geographic location, use of sunscreen, darker skin pigmentation, obesity, and dietary habits can all decrease the body's ability to maintain adequate vitamin D levels. Reproductive health providers emphasize the importance of addressing these modifiable factors through personalized advice, encouraging safe outdoor activity and appropriate dietary choices to enhance vitamin D synthesis and absorption.

Holistic fertility support

Incorporating vitamin D management into fertility care represents a holistic approach to reproductive health. This strategy includes screening and correcting vitamin D deficiency alongside monitoring reproductive hormones, ovarian reserve, and providing psychological support. By addressing vitamin D status as a part of an overall fertility health plan, clinicians aim to improve menstrual regularity, ovulation, endometrial receptivity, and ultimately pregnancy rates.

Such multidisciplinary care enhances patient outcomes by combining medical treatments with nutritional and lifestyle optimization, fostering a supportive environment for conception and maternal-fetal health.

Vitamin D in the Context of Common Fertility Treatments and ART

What is the relationship between vitamin D and common fertility treatments including ART?

Vitamin D plays a significant role in enhancing the outcomes of fertility treatments such as assisted reproductive technologies (ART), including in vitro fertilization (IVF). Adequate vitamin D levels improve ovarian function by acting on vitamin D receptors (VDRs) found in granulosa cells, promoting hormone regulation, follicular development, and ovulation. This supports a more responsive ovarian environment to fertility medications.

Beyond ovarian effects, vitamin D also influences endometrial receptivity, crucial for embryo implantation. Women with sufficient vitamin D levels show increased endometrial thickness at the time of human chorionic gonadotropin (HCG) administration, correlating with higher implantation and clinical pregnancy rates. Studies have reported that vitamin D sufficiency boosts clinical pregnancy rates in IVF/ICSI treatments by improving factors like the number of retrieved oocytes and embryo quality.

Interaction of vitamin D with fertility medications

Vitamin D enhances the efficacy of fertility drugs by modulating the hypothalamic-pituitary-gonadal axis and improving estrogen synthesis through increased aromatase activity. This hormonal balance helps in normalizing menstrual cycles and ovulation, which in turn potentiates the response to ovulation induction agents and controlled ovarian stimulation protocols used in ART.

Enhancement of ART outcomes by optimizing vitamin D

Research supports that serum vitamin D concentrations above 30 ng/mL are associated with better reproductive outcomes, including higher clinical pregnancy and live birth rates in women undergoing fertility treatments. Supplementation in deficient women leads to improved ovarian reserve markers such as anti-Müllerian hormone (AMH) and antral follicle count (AFC), and better endometrial development.

Vitamin D as an adjunct therapy

Considering its safety, low cost, and favorable effects on reproductive tissue function, vitamin D supplementation is increasingly recognized as a beneficial adjunct in fertility treatment protocols. Typical supplementation doses range from 1,000 to 10,000 IU daily, tailored according to baseline serum levels. Adjunct vitamin D use has shown to reduce infertility associated with conditions like polycystic ovary syndrome (PCOS) by improving menstrual regularity and insulin sensitivity.

Integrating vitamin D status monitoring and supplementation into standard fertility care may improve assisted reproduction success rates and overall pregnancy outcomes without substantial risks or costs. Further high-quality randomized controlled trials are warranted to refine dosing protocols and maximize therapeutic benefits.

Future Directions: Research and Clinical Implications for Vitamin D in Reproductive Health

What are the future research needs regarding vitamin D’s role in reproductive health?

Current research highlights a strong association between adequate vitamin D levels and improved reproductive outcomes, including enhanced fertility, better assisted reproductive technology success rates, and reduced pregnancy complications. However, despite compelling observational and some intervention data, there remains a need for more high-quality randomized controlled trials (RCTs) to clarify these relationships.

Large-scale, well-designed RCTs are essential to precisely define optimal serum vitamin D thresholds during preconception and pregnancy stages that maximize reproductive success. These studies should also investigate the most effective supplementation protocols—considering dosage, duration, and administration frequency—to safely enhance fertility and minimize adverse outcomes.

Furthermore, research exploring the interplay between vitamin D status and individual patient factors such as genetics, baseline levels, and comorbid conditions like PCOS will enable tailoring of treatments.

Advancing this evidence base could transform clinical practice, facilitating personalized fertility care. Such approaches would integrate vitamin D monitoring and targeted supplementation as routine components of reproductive health management, ultimately improving pregnancy rates, reducing miscarriage risks, and lowering pregnancy complications.

Ongoing investigation will also inform guidelines for diverse populations, helping address socioeconomic and seasonal disparities in vitamin D status among women seeking conception and pregnancy support.

Vitamin D: A Vital Component of Fertility and Pregnancy Success

Vitamin D emerges as a multifaceted contributor to reproductive health, influencing everything from hormonal regulation and ovarian function to embryo implantation and pregnancy outcomes. Its deficiency is linked to significant fertility challenges and pregnancy complications, while supplementation demonstrates tangible benefits in improving conception rates, especially within assisted reproductive technologies. Recognizing and addressing vitamin D insufficiency should be incorporated into fertility care strategies for both women and men. As research continues to clarify optimal supplementation practices, vitamin D stands out as a safe, accessible, and impactful adjunct in the quest to support reproductive success and healthy pregnancies.

References

• The Key Role of Vitamin D in Female Reproductive Health
• Influence of Vitamin D supplementation on reproductive ...
• How Vitamin D May Impact Your Fertility
• Effects of Vitamin D on Fertility, Pregnancy and Polycystic ...
• Association of vitamin D intake and serum levels with fertility
• Vitamin D and assisted reproductive treatment outcome
• Vitamin D deficiency in a subfertility population and the impact ...
• Assessing vitamin D's impact on pregnancy success
• How Vitamin D Affects Your Fertility