Is medical research entering a new era of fertility treatments?

In this article, we delve into the history, current landscape, and future direction of fertility treatments, exploring the underlying science and recent advancements.

We will also gain some insights from a leading expert in the field, Dr. Piraye Yurttas Beim, Founder and CEO of Celmatix, a women's health biotech company focused on ovarian biology. 

They recently unveiled an innovative program that not only aims to eliminate the need for follicle-stimulating hormone (FSH) injections during IVF and egg freezing but also holds the potential to transform male infertility treatment by enhancing sperm count and viability.

A brief history of IVF

Infertility is not a recent issue, nor is it exclusive to humans. Several plant and animal species also have infertility problems. Over the centuries, different cultures have developed their own customs, beliefs, and remedies to address infertility.

The idea of artificial insemination was known as early as 3500 BC, as evidenced in India by Vedic literature. During this period, traditions like Niyoga pratha sometimes enabled individuals who did not have children with their spouses to conceive a child with another man or woman in a socially acceptable manner.

Modern IVF (as well as modern birth control) got a boost in the 1920s, when medical researchers identified the female fertility hormones estrogen and progesterone. In 1943, hormone supplements were developed. These fertility supplements and drugs allowed doctors to boost the chances of pregnancy in patients as well as the ability to control and time egg development and ovulation, which are keys to the success of IVF.

IVF was first tested on mice and rabbits in the 1950s, and by the early 1970s researchers felt confident enough of the techniques to begin focusing on replicating the IVF treatment process in humans.

At the same time, the idea of sperm preservation and banking emerged, leading to the development of cryopreservation techniques. This advancement not only facilitated artificial insemination but also played a crucial role in the development of IVF procedures, where preserved sperm could be thawed and utilized in the process of fertilizing eggs outside the human body.

During the mid-20th century, artificial insemination techniques set the stage for advancements in IVF. Dr. Patrick Steptoe and Sir Robert Edwards emerged as IVF pioneers, with the birth of the first test tube baby in 1978 marking a significant milestone in the field.

Since that time, IVF has become relatively common for addressing fertility issues. This procedure involves using hormone therapy to stimulate the ovaries to produce multiple eggs, which are then retrieved and fertilized with sperm in a laboratory.

Advancements in fertility treatments

Cryopreservation

Cryopreservation was a significant advancement in fertility treatments in allowing women to preserve their fertility for later stages of life. Oocyte cryopreservation, also known as egg freezing, involves extracting and freezing unfertilized eggs from a woman's ovaries. 

This method can offer women the opportunity to delay pregnancy without the concern of declining egg quality associated with advanced maternal age. It can also preserve eggs in the case of ovarian cancer, when the eggs may be destroyed through radiation therapy.

The cryopreserved eggs can be thawed and fertilized later through IVF.

Sperm cryopreservation is also used in fertility treatment. This involves freezing and storing sperm samples for later use. This process is especially beneficial for men who face issues like infertility due to medical treatments, surgery, or other factors. 

Intracytoplasmic sperm injection (ICSI)

ICSI represents another key advancement in fertility treatments, particularly for cases of male infertility. It involves the injection of a single sperm into an egg to aid in fertilization.

This technique has been used in the treatment of severe male infertility conditions, such as non-obstructive azoospermia (NOA), where sperm is absent in the semen.

Recent developments in ICSI include using artificial intelligence (AI) to aid in the selection of the best sperm for injection, optimizing the chances of successful fertilization and healthy embryo development.

Stem cell therapy

The emergence of stem cell treatments in the field of fertility is another new development. Stem cell therapies hold the potential to repair damaged tissues and cells, offering renewed hope for addressing infertility caused by various medical conditions.

Artificial intelligence (AI)

AI has introduced sophisticated algorithms that can aid in the selection of embryos with higher chances of successful implantation. This approach uses AI to make more accurate predictions and to streamline processes, such as rapidly and accurately identifying sperm in severely infertile men.

According to Dr. Beim, Celmatix has successfully used AI in their drug discovery efforts. “Our pipeline of drugs is a result of leveraging data to highlight the most promising opportunities,” Dr. Beim explained to Interesting Engineering (IE), citing AI's pivotal role in advancing their oral gonadotropin program.

The burden on women

Despite the strides in fertility treatments, it remains evident that a substantial burden for fertility continues to fall on women. Cultural norms and societal pressures often equate womanhood with motherhood, magnifying the emotional toll experienced by those facing infertility. 

Even today, when many argue for the need to reduce population growth, there is still the expectation for many women that they will have children.

Dr. Beim addresses this issue by pointing out that studying infertility involves extended treatment protocols. "This increases the cost of developing drugs through longer clinical trials and also the timeline to a live birth outcome for individuals experiencing infertility," she noted. 

She further highlights the substantial market potential in addressing male infertility. "We believe many men would welcome reducing the treatment burden on their partners."

"Improving their sperm parameters could also have positive health effects and be a treatment by-product, which isn't the case for women using IVF due to their partner's infertility," she explained.

The availability of an oral therapy that is safe and effective for male infertility treatments arising due to low sperm count could help shift the burden of medical care, as well as of expectation.

Underscoring the intricate relationship between reproductive health, social dynamics, and gender-based violence, a recent article in The Lancet Global Health sheds light on the prevalence of partner violence among infertile women in low- and middle-income countries.

While advancements in fertility treatments have opened new possibilities for conception, it is crucial to address the underlying gendered aspects that perpetuate unequal expectations and pressures. 

This brings us to Celmatix and their recent announcement that could help alleviate the burden on women.

Eliminating injections

FSH is an important hormone that regulates the growth and development of ovarian follicles in women, leading to the release of mature eggs during ovulation. In men, FSH stimulates the production of sperm within the testes. In simple terms, FSHRs are detectors in the reproductive system which respond to the FSH hormone to help with reproduction. 

Consequently, FSH receptors (FSHR) play a vital role in the reproductive system, responding to follicle-stimulating hormone (FSH). Manipulating FSHRs can profoundly impact fertility outcomes, making them a critical target for fertility treatments.

Celmatix is working to develop the first oral FSHR agonist drug. This drug aims to trigger the FSHRs in a controlled manner and in doing so, mimic the effects of the naturally occurring follicle-stimulating hormone FSH in the body.

Their program hopes to achieve two main goals: firstly, to eliminate the requirement for injections during ovarian stimulation for IVF and egg freezing; and to decrease the necessity for IVF treatments by improving ovulation induction and directly addressing male infertility.

Addressing their goals, Dr. Beim said, "Injectable fertility drugs burden patients and providers during IVF, in terms of counseling and financial costs. Celmatix's oral medication could transform fertility treatments significantly."

Explaining the advantages compared to traditional fertility drugs, Dr. Beim explained, "Women prefer treatments without injections if safety isn't compromised. Animal studies suggest oral gonadotropins, such as FSH, could offer similar outcomes and better safety due to a wider therapeutic window."

Celmatix aims to initiate clinical studies by 2025. To this end, the company is working with contract research organizations (CROs) and academic partners to expedite the FDA trials necessary for regulatory approval.

Future research

The future of some other fertility treatments also looks promising, as new avenues open up. 

"The complexity and risks of current oral gonadotropin protocols demand specialized reproductive endocrinology expertise for IVF-related egg maturation. Safer oral drugs with standard protocols, reducing IVF reliance, will enable broader provider access," explained Dr. Beim.

Dr. Beim also emphasized the need to shift the burden of infertility treatment solely from women to a more balanced approach. "The availability of an orally active therapy that is safe and effective for male infertility treatments due to low sperm count would shift rather than always placing the responsibility on the female partner," she explained. 

Taking these factors into consideration is crucial for future research.

A study led by J.M.N. Duffy from University College London emphasizes the importance of prioritizing areas such as the impact of male reproductive health on fertility, finding preventive measures for age-related infertility, refining assisted reproductive techniques, and tackling the emotional toll of treatment failures. 

Additionally, ethical concerns regarding affordability and access to fertility treatments also warrant significant attention. 

Moreover, scientists are actively developing techniques that help make the process easier for the individuals involved, with ongoing research focusing on safer oral fertility drugs, improved treatment accessibility, and addressing emotional well-being throughout the fertility journey.