Medications

What medications are used for ovulation induction?

There are several medications used for ovulation induction, each with specific mechanisms of action and particular clinical applications. Clomiphene citrate is one of the most commonly used drugs, administered orally for 5 consecutive days at the start of the menstrual cycle. This medication blocks estrogen receptors in the hypothalamus, leading to an increase in gonadotropin release.

Gonadotropins are another important group of medications used in ovarian induction. These hormones, such as recombinant FSH or human menopausal gonadotropin (HMG), are administered subcutaneously and act directly on the ovaries, stimulating follicular development. Its use requires a hormonal monitoring and more intensive ultrasound due to its power.

Initially developed as a treatment for breast cancer, letrozole is also used as an ovulation inducer, especially in patients with polycystic ovary syndrome. It works by inhibiting estrogen production, which causes an increase in the secretion of FSH by the pituitary gland.

What side effects can occur with these treatments?

Medications for the induction of ovulation can cause a variety of side effects that vary in frequency and intensity depending on the drug used and the individual sensitivity of each patient. With clomiphene citrate, the most common side effects include hot flashes, mood changes, breast tenderness, and vaginal dryness, usually mild and transient.

Gonadotropins can be associated with side effects such as abdominal pain, bloating and ovarian hyperstimulation syndrome, a potentially serious complication that requires immediate medical attention. This syndrome is characterized by an increase in ovarian size, fluid accumulation in the abdomen and electrolyte disturbances.

Letrozole usually causes fewer side effects than clomiphene, but it may cause fatigue, dizziness and headaches in some patients. According to data from the National Institute of Health of Mexico, less than 10% of patients experience significant side effects that require discontinuation of treatment.

How do you determine which medication is right for each patient?

The choice of the most appropriate medication for each patient is based on multiple clinical and personal factors. Reproductive medicine specialists consider:

• Specific cause of infertility
• Medical history and response to previous treatments
• Age of the patient
• Body mass index
• Hormone test results such as AMH test
• Presence of comorbidities
• Personal preferences regarding the route of administration

The doctor also evaluates the ovarian reserve using specific tests to determine the starting dose and treatment protocol. Young patients with polycystic ovary syndrome usually start with oral medications such as clomiphene or letrozole, while older patients or patients with low ovarian reserve may benefit more from gonadotropins.

What is the usual protocol for administering these drugs?

The administration protocol varies depending on the medication used and the characteristics of each patient. For clomiphene citrate, the typical schedule is to take a dose of 50-100 mg daily for five consecutive days, starting on the second or third day of the menstrual cycle. If ovulation is not achieved, the dose may be gradually increased in subsequent cycles.

With gonadotropins, the protocol is more complex and personalized. It usually starts with a low dose (75-150 IU daily) given as subcutaneous injections for 7-12 days. The dose is adjusted according to the ovarian response, monitored by transvaginal ultrasound and serial hormone analysis.

For letrozole, the usual schedule is 2.5-7.5 mg daily for five days at the start of the cycle. La follicular monitoring ultrasound is performed starting on day 10-12 of the cycle to evaluate follicular development and schedule sexual intercourse or additional procedures such as artificial insemination.

What recent advances are there in medications for ovarian induction?

In recent years, research in the field of reproductive medicine has made it possible to develop new drugs and optimize existing protocols. One of the most significant innovations has been the development of gonadotropin biosimilars, which offer the same efficacy as the original products at a more affordable cost.

Another important area of progress is the use of anti-Müllerian hormone as a marker to personalize gonadotropin doses, allowing for more precise stimulation and reducing the risk of ovarian hyperstimulation. According to studies published in the journal Fertility and Sterility, this personalized approach has improved success rates and reduced complications (Trusted Source).

Researchers are also exploring the potential of next-generation selective estrogen receptor modulators, which could offer better safety and efficacy profiles than traditional medications. These new therapeutic options promise to expand the arsenal of treatments available for female fertility tests.

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Procedure

How is ovulation induction performed step by step?

The ovulation induction procedure follows a structured protocol that begins with a detailed evaluation of the patient. Initially, the specialist performs a complete physical examination and requests basic hormonal tests, preferably during the first days of the menstrual cycle, to evaluate ovarian function and detect possible causes of infertility.

Once the diagnosis has been established, the most appropriate medication protocol is selected. During treatment, the patient undergoes regular check-ups to monitor follicular development through transvaginal ultrasound. These reviews usually start around day 10 of the cycle and may be repeated every 2-3 days depending on the ovarian response.

When the follicles reach an optimal size (usually 18-20 mm), an injection of human chorionic gonadotropin (hCG) can be administered to trigger ovulation, which will occur approximately 36-40 hours later. At that time, directed intercourse or artificial insemination to maximize the chances of conception.

What types of monitoring are used during treatment?

Monitoring during ovarian induction treatment is essential to ensure its effectiveness and safety. The main methods of follow-up include serial transvaginal ultrasound that allows us to visualize the number and size of developing follicles, as well as the thickness of the endometrium, a crucial factor for embryo implantation.

Hormonal tests complement the ultrasound evaluation by measuring serum estradiol, which reflects the activity of growing follicles. In some cases, progesterone is also monitored to confirm ovulation. This combined monitoring allows medication doses to be adjusted according to the individual response and to determine the optimal time to trigger ovulation.

In more complex cases, especially when gonadotropins are used, monitoring may also include luteinizing hormone evaluations to detect endogenous peaks that could interfere with scheduled treatment. This entire process requires smooth communication between the patient and the medical team of Fertility.

How long does an ovarian induction cycle usually last?

The length of an ovarian induction cycle varies depending on the protocol used and the individual response of each patient. Typically, a full cycle ranges from the start of medication to the confirmation of ovulation or treatment failure, usually lasting between 2 and 4 weeks.

For treatments with clomiphene citrate or letrozole, stimulation usually starts in the first few days of the menstrual cycle and continues for 5 days. Ovulation usually occurs between days 14 and 18 of the cycle. In gonadotropin protocols, the stimulation phase can be extended up to 12-14 days, with frequent monitoring starting on day 6-7 of stimulation.

It is important to consider that many patients require several cycles of treatment before achieving pregnancy. Most specialists recommend evaluating the response after 3-4 cycles to determine if it is necessary to modify the therapeutic approach or consider other assisted reproduction techniques such as FIV-ICSI.

When is ovarian induction treatment considered successful?

The success of an ovarian induction treatment can be evaluated at different levels. The first indicator of success is ultrasound and hormonal confirmation that ovulation has occurred, indicating that the primary goal of treatment has been achieved. However, the real purpose of treatment is to achieve a viable pregnancy.

Specialists consider treatment successful when a clinical pregnancy is achieved confirmed by ultrasound, with visualization of the gestational sac and cardiac activity. Success rates vary considerably depending on the cause of infertility, patient age and protocol used, ranging from 15% to 40% per treated cycle.

It is important to maintain realistic expectations, as factors such as oocyte quality, endometrial receptivity and sperm quality also influence the final result. Some centers offer complementary options such as freezing of embryos to optimize the chances of success.

What follow-up is done after completing the treatment cycle?

After completing an ovarian induction cycle, personalized follow-up is carried out to evaluate the results and plan the next steps. Approximately 14 days after confirmed ovulation, a blood pregnancy test (beta-hCG) is performed to determine if conception has been achieved.

In case of a positive result, a transvaginal ultrasound is scheduled about 2-3 weeks later to confirm the viability of the pregnancy and rule out multiple pregnancies, a risk associated with ovarian induction. If the result is negative, the specialist evaluates the response to the treatment and decides whether to keep the same protocol or make adjustments for the next cycle.

Throughout the follow-up process, emotional support for the patient is essential, since fertility treatments can generate considerable stress and anxiety. Many centers offer psychological support services specifically designed for patients undergoing assisted reproduction treatments.

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Risks

What are the main risks associated with ovarian induction?

The induction of ovulation, like any medical intervention, involves certain risks that must be considered before starting treatment. El ovarian hyperstimulation syndrome (SHO) represents the most significant risk, especially when gonadotropins are used. This complication is characterized by an excessive increase in ovarian size, fluid accumulation in the abdominal cavity and, in severe cases, electrolyte disturbances and cardiovascular involvement.

Another significant risk is the increased likelihood of multiple pregnancies, which occurs due to the stimulation of several follicles simultaneously. Multiple pregnancies are associated with higher rates of maternal and neonatal complications, including preterm delivery and low birth weight.

There is also a small risk of ovarian torsion due to an increase in the size of the ovaries during treatment. Although rare, this complication requires urgent surgical intervention to preserve ovarian function. According to data published by the Latin American Federation of Fertility Societies, the incidence of serious complications is less than 1% when adequate follow-up is carried out.

How is the risk of ovarian hyperstimulation syndrome minimized?

To minimize the risk of ovarian hyperstimulation syndrome, specialists implement various preventive strategies. Identifying patients with risk factors, such as young age, polycystic ovary syndrome, low body mass index or a history of exaggerated response, allows for more conservative protocols to be adopted from the start.

The use of low doses of gonadotropins and their gradual adjustment according to the ovarian response is an essential preventive measure. Intensive monitoring using frequent ultrasound and hormonal determinations can detect early signs of hyperstimulation and modify treatment before serious complications develop.

In patients with an excessive response, it is possible to cancel the cycle, freeze all embryos for subsequent transfer when the ovaries have regained their normal size, or replace hCG with GnRH agonists to trigger ovulation, a strategy that has been shown to significantly reduce the risk of hyperstimulation without compromising success rates in programs of in vitro fertilization.

What specific risks are there for patients with polycystic ovary syndrome?

Patients with polycystic ovary syndrome (PCOS) have special considerations during ovarian induction due to their increased sensitivity to stimulant medications. These patients have an increased risk of developing ovarian hyperstimulation syndrome and multiple pregnancies, so they require protocols adapted to their condition.

The risk of resistance to clomiphene citrate is also higher in this group, affecting up to 20% of patients. In these cases, it is necessary to consider alternatives such as letrozole, which has demonstrated greater effectiveness and a lower rate of multiple pregnancies in women with PCOS according to recent studies.

Additionally, these patients are more likely to have spontaneous abortions, in part due to metabolic disorders associated with the syndrome. Implementing complementary measures such as lifestyle modifications, weight control, and treatment of insulin resistance can significantly improve treatment outcomes and reduce associated risks.

How does the patient's age affect the risk of treatment?

The patient's age is a determining factor in the risk-benefit balance of ovarian induction. Younger patients tend to respond more intensely to hormonal stimulation, increasing the risk of ovarian hyperstimulation syndrome and multiple pregnancies. Therefore, more conservative protocols are recommended in these patients, with lower initial doses and close monitoring.

In contrast, elderly patients (over 37-38 years old) have a lower risk of hyperstimulation, but also lower success rates due to the natural decrease in oocyte reserve and quality. In this age group, the main risk is the low response to treatment and the increased likelihood of chromosomal abnormalities in the resulting embryos.

In older patients, it may be necessary to consider complementary options such as egg donation to increase the chances of success. According to data from the American Society for Reproductive Medicine, the rate of live births with their own eggs decreases significantly after age 40, regardless of the type of treatment used.

What long-term complications could there be?

Although most of the effects of ovarian induction treatment are transient, there is debate about potential long-term complications. Epidemiological studies have not demonstrated a significant increase in the risk of ovarian cancer in patients undergoing these treatments, according to the most recent review by the International Fertility Society.

However, some researchers recommend caution in patients with pre-existing risk factors for hormone-dependent cancer or a significant family history. In these cases, it may be preferable to limit the number of stimulation cycles and to consider techniques of preservation of fertility alternatives.

Psychological complications represent another area of long-term concern. The stress associated with fertility treatments, especially when they are prolonged or unsuccessful, can have lasting effects on patients' emotional well-being. Therefore, psychological support is increasingly seen as an essential component of comprehensive infertility treatment.

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Alternatives

What options are there when ovulation induction doesn't work?

When ovulation induction fails to achieve the expected results after several cycles, there are several therapeutic alternatives. The next step is usually the in vitro fertilization (IVF), a more complex procedure that involves controlled ovarian stimulation, the extraction of eggs through follicular puncture, their fertilization in the laboratory and the subsequent transfer of embryos to the uterus.

In cases of low ovarian response or compromised oocyte quality, especially in elderly patients, the option of IVF with donor eggs offers excellent success rates. This procedure allows the patient to experience pregnancy and childbirth, using eggs from an anonymous younger donor.

For couples with severe male factor who have not responded to ovarian induction combined with artificial insemination, the ICSI (intracytoplasmic sperm injection) technique allows direct fertilization of the egg in the laboratory, overcoming many of the barriers that prevent natural fertilization.

How does ovarian induction compare to other assisted reproduction techniques?

Ovulation induction is generally considered the first therapeutic step in the treatment of infertility due to ovulatory causes, being less invasive and costly than other assisted reproduction techniques. Compared to in vitro fertilization, ovarian induction involves fewer medical interventions, less use of medications, and a lower emotional and economic burden.

However, the success rates of ovarian induction are generally lower than those of IVF, especially in patients with multiple factors of infertility or advanced age. While ovarian induction with directed intercourse or artificial insemination can achieve pregnancy rates of 15-20% per cycle, IVF can exceed 40% under optimal conditions.

Another important difference is the possibility of performing pre-implantation genetic diagnosis in IVF procedures, which allows embryos free of certain genetic anomalies to be selected before their transfer to the uterus, an option not available in conventional ovarian induction treatments.

What complementary treatments can improve the success of ovarian induction?

Various complementary treatments can optimize the results of ovarian induction in selected cases. Metformin has been shown to improve response to treatment in patients with polycystic ovary syndrome and insulin resistance, increasing ovulation rates and reducing the risk of spontaneous abortion.

Nutritional supplements such as folic acid, vitamin D and antioxidants can help improve oocyte quality and endometrial receptivity. Although scientific evidence is variable, these supplements are generally considered safe and potentially beneficial, especially in patients with documented deficiencies.

Complementary therapies such as acupuncture have been studied in the context of fertility treatments, with promising but not conclusive results. Some studies suggest that acupuncture may improve uterine perfusion and reduce stress associated with treatment, factors that could positively influence outcomes.

When is it recommended to move directly to more advanced techniques?

Under certain circumstances, specialists may recommend omitting ovarian induction and proceeding directly to more advanced techniques such as in vitro fertilization. This mainly occurs when there are additional factors that compromise fertility, such as:

• Bilateral tubal obstruction
• Severe male factor
• Moderate or severe endometriosis
• Advanced maternal age (>38 years)
• Low ovarian reserve confirmed
• Multiple previous failures with less complex techniques

The decision to move directly to more sophisticated techniques is based on maximizing the chances of success and minimizing the time until pregnancy. This is particularly relevant in elderly patients, where the time factor is critical. Some centers offer options such as frozen egg bank for patients who require gamete donation.

What role do natural therapies play in treating ovulatory problems?

Natural therapies can play a complementary role in managing ovulatory problems, although scientific evidence on their efficacy is variable. Lifestyle modifications, particularly the normalization of body weight, have been shown to significantly improve ovulatory function in overweight or obese patients associated with ovarian dysfunction.

Regular moderate physical activity and stress management techniques such as mindfulness or yoga can help regulate menstrual cycles and improve response to treatment, possibly by modulating levels of cortisol and other stress-related hormones.

Some herbal supplements such as raspberry leaf tea, black cohosh or maca have traditionally been used to regulate menstrual cycles, although scientific evidence on their efficacy is limited and it is recommended to consult a specialist before using them during ovarian induction treatment to avoid possible interactions.

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Candidates

Who are the ideal candidates for ovulation induction?

Ideal candidates for ovulation induction are women with confirmed ovulatory dysfunction but who maintain tubal permeability and basic ovarian function. Patients with anovulation or oligoovulation secondary to polycystic ovary syndrome represent the group with the best response rates to treatment, especially when they are under 35 years of age and have no other associated infertility factors.

Women with hypothalamic amenorrhea secondary to weight loss, excessive exercise, or stress also tend to respond favorably to ovarian induction protocols, once the triggers have been corrected. Mild to moderate hyperprolactinemia treated appropriately with dopaminergic agonists is another group with a good prognosis.

Patients with premature ovarian failure or early menopause are generally not good candidates for these treatments, as they have very little or no follicular reserve. In these cases, alternatives such as egg donation are usually more appropriate.

What evaluations should be performed before starting treatment?

Before starting ovarian induction treatment, a comprehensive evaluation is essential to confirm the diagnosis, identify the underlying cause, and rule out conditions that could contraindicate treatment. The diagnostic process usually includes:

A detailed medical history that explores gynecological, obstetric, medical and family history, and lifestyle habits that may affect fertility. The complete physical exam should include evaluation of body mass index, body hair distribution, and development of secondary sexual characteristics.

Las hormonal tests Basics include FSH, LH, estradiol, prolactin and anti-Müllerian hormone (AMH) to evaluate ovarian reserve. Depending on the clinical context, additional tests such as testosterone, DHEAS, TSH, or cortisol may be ordered to identify specific endocrine disorders.

The evaluation of tubal permeability using hysterosalpingography or hysterosonography is essential, since tubal obstruction would limit the effectiveness of simple ovarian induction. In addition, it is recommended to perform an at least basic seminogram on the male partner to rule out significant male factors.

How do comorbidities affect treatment success?

Various comorbidities can significantly influence the success of ovarian induction treatment and the risk of associated complications. Obesity negatively affects both response to treatment and pregnancy rates, due to alterations in hormonal metabolism and the higher prevalence of insulin resistance. It is recommended to attempt weight reduction before starting treatment in patients with a BMI greater than 30.

Uncontrolled thyroid diseases, particularly hypothyroidism, can compromise ovarian response and increase the risk of complications during pregnancy. The normalization of thyroid function must precede the onset of ovarian induction.

Diabetes mellitus, especially when it is not adequately controlled, can negatively affect oocyte quality and endometrial receptivity. Diabetic patients require a thorough metabolic evaluation and optimization of glycemic control before and during treatment of Fertility.

What are the absolute contraindications for this treatment?

There are clinical situations that constitute absolute contraindications for the induction of ovulation due to the unacceptable risk they would pose to the patient's health. Among them, the following stand out:

An established pregnancy should always be ruled out before starting any hormonal treatment. Hormone-dependent tumors such as breast, endometrial or ovarian cancer represent absolute contraindications for the administration of medications that increase levels of circulating estrogen.

Active thrombosis or uncontrolled states of hypercoagulability contraindicated the use of medications that may further increase thrombotic risk, such as ovulation inducers. Large or undiagnosed functional ovarian cysts must resolve before starting ovarian stimulation.

Patients with severe hepatic or renal impairment are not suitable candidates due to the altered metabolism of the drugs used. Also, those with atypical endometrial hyperplasia or undiagnosed abnormal uterine bleeding should postpone treatment until these conditions resolve.

What psychosocial factors influence the decision to start this treatment?

Psychosocial factors play a fundamental role in the decision to initiate ovarian induction treatment and can significantly influence the experience and results of the treatment. The stability of the couple's relationship and mutual support during the process are elements that predict better tolerance to the stress associated with fertility treatments.

Religious or cultural beliefs may influence the acceptance of certain procedures or the management of complications such as multiple pregnancies. Open communication on these aspects makes it possible to develop a treatment plan that respects the values of each patient.

Realistic expectations about the chances of success and the duration of treatment are essential to minimize frustration and premature abandonment. Specialists should spend sufficient time clearly explaining the specific success rates for each particular case and the number of cycles that might need to be tried before considering alternatives.

Future

What are the most promising innovations in ovulation induction?

The field of ovarian induction continues to evolve with promising innovations that could improve both the efficacy and safety of treatments. Pharmacogenomics represents one of the most interesting areas, seeking to identify genetic markers that allow predicting the individual response to different medications and customizing protocols from the start, minimizing the time needed to achieve the optimal dose.

The development of new GnRH agonists and antagonists with optimized pharmacokinetic profiles promises to reduce side effects while maintaining or improving efficacy. These new drugs could simplify current protocols and make them more tolerable for patients.

Advances in imaging techniques, such as three-dimensional ultrasound with automated antral follicle count analysis, are improving accuracy in evaluating ovarian reserve and monitoring response to treatment. These tools allow for more precise medication adjustments and better timing of complementary procedures.

How is artificial intelligence influencing this field?

Artificial intelligence is beginning to transform various aspects of reproductive medicine, including the induction of ovulation. Machine learning algorithms applied to large clinical databases are identifying patterns that allow us to predict with greater precision which patients will respond best to certain protocols, optimizing initial treatment selection.

In the area of monitoring, systems based on artificial intelligence can analyze ultrasound images to automatically evaluate follicular development and endometrial quality, providing more objective and reproducible measurements. These systems could reduce inter-observer variability and improve monitoring consistency.

Predictive models based on multiple clinical, hormonal and ultrasound variables are improving the ability to predict the risk of ovarian hyperstimulation syndrome, allowing personalized preventive strategies to be implemented. According to experts from the European Society for Human Reproduction, these tools could revolutionize treatment safety in the coming years.

What role will stem cell therapies play in the future of this treatment?

Stem cell research represents one of the most exciting frontiers in the field of reproductive medicine. Although still in experimental phases, therapies based on ovarian stem cells could potentially revolutionize the treatment of female infertility, especially in cases of low ovarian reserve or premature ovarian failure.

Preliminary studies have shown that certain stem cell populations can stimulate ovarian tissue regeneration and potentially increase follicular reserve. These techniques could complement or even replace conventional ovarian induction protocols in selected patients, offering an alternative that is less dependent on exogenous hormonal medication.

However, experts warn that more research is needed to confirm the safety and efficacy of these therapies before their routine clinical implementation. The current consensus is that, while promising, these technologies will probably take at least a decade to become available as standardized treatments.

Where is research on drugs for ovarian induction heading?

Research in drugs for ovarian induction is currently oriented towards the development of more selective drugs with improved safety profiles. A promising line is that of next-generation selective estrogen and progesterone receptor modulators, designed to act specifically on reproductive tissues, minimizing systemic effects.

Researchers are also exploring alternative ways for ovarian stimulation, such as compounds that act on specific ovarian growth factors or intracellular signaling, seeking to selectively stimulate follicular development without causing the hormonal imbalances associated with conventional treatments.

The inclusion of ovarian response biomarkers in clinical trials of new drugs is making it possible to identify subpopulations of patients who could particularly benefit from certain compounds, moving towards a personalized medicine paradigm in assisted reproduction that optimizes results and minimizes adverse effects.

How might the monitoring of these treatments evolve in the future?

The monitoring of ovarian induction treatments is evolving towards less invasive and more precise modalities that will allow for more comfortable monitoring for patients and more informed decision-making for clinicians. Portable devices for home hormone measurement could significantly reduce the number of hospital visits needed during a treatment cycle.

Advanced imaging techniques, such as ovarian functional magnetic resonance imaging or new modalities of ultrasound with automated analysis, promise a more accurate assessment of follicular development and endometrial receptivity. These advances would allow finer medication adjustments and better personalization of the optimal time for scheduling sexual intercourse or complementary procedures.

Telemedicine and specific mobile applications for monitoring fertility treatments are facilitating more fluid communication between patients and professionals, allowing continuous monitoring of symptoms and side effects, as well as more agile therapeutic adjustments when necessary. This modality could be especially beneficial for patients in rural areas or who have difficulty going to the clinic frequently.

What changes are anticipated in clinical guidelines for ovarian induction?

Clinical guidelines on ovarian induction are constantly evolving to incorporate the most recent scientific evidence and technological innovations. A clear trend is the progressive individualization of protocols, abandoning rigid schemes in favor of personalized approaches based on multiple clinical, hormonal and ultrasound parameters.

A greater emphasis is expected on strategies for the prevention of ovarian hyperstimulation syndrome, with more specific recommendations on when to use alternative protocols such as GnRH antagonists with agonist triggers or total embryo freezing in high-risk patients, procedures that may be part of the freezing of embryos.

Future guidelines will probably also incorporate more information on the management of specific populations, such as transgender or non-binary patients who want to preserve their fertility, reflecting the growing diversity of people seeking access to assisted reproduction services and the need for approaches adapted to their particular circumstances.

References

1. González-Comadran, M., Schwarze, J.E., Zegers-Hochschild, F., Souza, M.D., Carreras, R., & Checa, M.Á. (2021). The impact of endometrial thickness on the success of ovulation induction with letrozole. Reproductive BioMedicine Online, 43 (3), 479-485. https://doi.org/10.1016/j.rbmo.2021.05.016 Trusted Source.
2. Palomba, S., Falbo, A., & La Sala, G.B. (2023). Metformin in women with polycystic ovary syndrome for improving fertility. Cochrane Database of Systematic Reviews, 2023 (4), CD008575. https://doi.org/10.1002/14651858.CD008575.pub4 Trusted Source.
3. World Health Organization. (2022). WHO laboratory manual for the examination and processing of human semen, 6th edition. WHO Press. https://www.who.int/publications/i/item/9789240030787 Trusted Source.

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