In recent years, infertility has become a widespread issue, impacting many individuals either personally or through someone they know. Statistics reveal that approximately 1 in 10 women in the United States aged 15-44 face fertility challenges, as reported by the CDC’s National Survey of Family Growth. Many of these women pursue fertility treatments to assist in conception and to uncover the underlying causes of their infertility. However, numerous questions remain unanswered, and, in some instances, the reasons for infertility are unexplained. Research in this area has not kept pace with the pressing clinical needs.

Kenneth Ward, who serves as an Advisor, Laboratory Director, and Medical Geneticist at Predictive Laboratories, and is also the Founder and CEO of Juneau Biosciences, shared his concerns with BioSpace: “As a practicing OBGYN and specialist in high-risk pregnancies, I noticed a troubling frequency of pregnancy complications. Transitioning to a full-time research role revealed just how little we understand about human reproduction and the slow progress of genetic testing technologies in this field.”

Yan Zhang, the Vice President and General Manager of Reproductive Health at Thermo Fisher Scientific, expressed to BioSpace, “Our aim is to enhance reproductive health, including addressing infertility issues. Predictive is poised to utilize its clinical and research capabilities alongside Thermo Fisher’s advanced technology and testing resources.”

Understanding the Causes of Infertility

One prevalent factor contributing to female infertility is endometriosis, which affects nearly 40% of women experiencing infertility. This condition occurs when tissue similar to the endometrium, which normally lines the uterus, develops outside of it, often impacting areas such as the ovaries, bladder, and intestines. This endometrial-like tissue still reacts to hormonal changes, leading to growth, bleeding, and shedding similar to the tissue inside the uterus. Consequently, the surrounding normal tissues can become inflamed and develop scar tissue, known as adhesions. This inflammation and scarring can lead to chronic pain before and during menstruation, heavy menstrual bleeding, and pain during intercourse or urination, although some women with endometriosis may be asymptomatic.

The damage from inflammation and scarring associated with endometriosis can also hinder fertility by affecting sperm or egg function and causing blockages in the fallopian tubes.

While the exact cause of endometriosis is unclear, several potential factors have been proposed, including issues with menstrual flow, genetic predisposition, hormonal imbalances, and immune system responses that fail to eliminate misplaced endometrial tissue. The familial tendency for endometriosis suggests a genetic component, making the search for genetic biomarkers particularly promising.

Research into how endometriosis affects fertility remains a significant focus in the field of infertility studies.

Research Landscape for Infertility and Endometriosis

Currently, the only conclusive method for diagnosing endometriosis is through a surgical procedure called laparoscopic surgery, where doctors look for and biopsy endometrial tissue outside the uterus. This invasive and costly method can lead to delays in diagnosis, negatively impacting both disease progression and the quality of life for affected women.

Creating a non-invasive diagnostic option, such as a blood test, is a priority for improving the diagnosis, management, and prognosis of endometriosis, according to G David Adamson, President of the World Endometriosis Research Foundation (WERF). However, the challenge lies in identifying reliable biomarkers for endometriosis, necessitating a better understanding of its causes and genetics, which remain elusive. Thus, current research is focused on two primary objectives: 1) identifying endometriosis biomarkers for a reliable blood test, and 2) exploring the genetic underpinnings of the condition.

A meta-analysis of 17 studies encompassing 1,279 patients published in May identified aromatase as a potential diagnostic biomarker, though it noted that “moderate quality” and small sample sizes limited definitive conclusions.

In July, new findings from a multiplex cytokine array evaluating 260 potential blood biomarkers in women with and without endometriosis were released. This high-throughput assay identified 14 serum cytokines that significantly differed between the two groups, with seven biomarkers uniquely associated with endometriosis patients.

In January, MDNA Life Sciences announced successful detection of endometriosis via blood samples from women with and without surgery-confirmed diagnoses. They found significant differences in mitochondrial DNA (mtDNA) between the two groups, achieving a reliable detection rate of 81.8% and 85.0%. This performance is comparable to the 60-85% accuracy of traditional diagnostic methods and boasts a high negative predictive value of 97%.

Notably, the smaller deletion in mtDNA was unaffected by hormonal changes or menstrual cycle variations, which typically complicate biomarker detection. However, further research with larger sample sizes is needed to validate these findings and clarify the role of the identified genes in endometriosis.

In April, MDNA Life Sciences announced plans to launch a blood test for detecting endometriosis biomarkers based on these mtDNA deletions, intending for clinical laboratories to utilize it.

Juneau Biosciences is investigating the genetic factors related to endometriosis through a study named End to Endo. This ongoing research has already involved tens of thousands of women, with a focus on those who have undergone gynecological surgeries due to pelvic pain or infertility. They employ genome-wide association studies, copy number analyses, and next-generation sequencing to identify reliable biomarkers for endometriosis.

“By unraveling the genetics of endometriosis, we aim to replace the need for surgical diagnosis with a non-invasive blood test and to identify biomarkers linked to an increased risk of certain cancers and autoimmune diseases,” Ward stated. “Our goal is to develop a blood test that can diagnose, classify the disease, and clarify the risks for each individual.”

In partnership with Predictive, Juneau has introduced a groundbreaking non-invasive test called ARTguide, which analyzes thousands of genetic variants related to endometriosis and 12 fertility-associated genes. This test helps predict a woman’s likelihood of having endometriosis based on her genetic risk factors and is designed for women considering assisted reproductive technologies like in vitro fertilization (IVF). ARTguide aims to provide crucial fertility insights, potentially reducing the number of cycles required for a successful pregnancy.

Advancing Research on Infertility through Collaboration

The ARTguide tests are integral to Predictive and Thermo Fisher’s collaborative research, with testing conducted using Thermo Fisher’s AmpliSeq technology. While all testing currently occurs in Predictive’s CLIA-regulated lab, there are plans to distribute test kits to other laboratories for broader accessibility. Initial rollouts have begun, with hopes of nationwide availability by year-end. Future aspirations also include adapting kits for international use, incorporating language translations and variations relevant to diverse populations.

Although Predictive and Thermo Fisher intend to explore various causes of female infertility, their initial focus will be on endometriosis due to the wealth of existing data. By leveraging Thermo Fisher’s advanced assays and next-generation sequencing, Predictive aims to investigate the genetic basis of endometriosis through whole exome sequencing.

Recently, Predictive presented its findings on the genetics of endometriosis at the European Society of Human Reproduction and Embryology (ESHRE) conference in June. They identified four mutated genes linked to women with surgically confirmed endometriosis. While only 8% of the general population carries these mutations, 25% of women with endometriosis possess at least one. This marks a significant step in understanding the genetic aspects of endometriosis, although the functions of the proteins encoded by these genes in the context of the disease remain unknown.

Originally published at https://www.biospace.com.