One of the greatest limitations in the creation of new fertility treatment paradigms is the fact that these studies require living subjects. Preliminary studies can be done on non-human primates, but ultimately, the efficacy and efficiency of fertility drugs is really not known until a human study is done. As a result, we truly have a dearth of options when it comes to treatment options for women who require ovarian stimulation and the pipeline from discovery to utilization is long and arduous. Well, that was until 2017.
Earlier this year, researchers at Northwestern University published the first fully-functioning female reproductive tract on a chip, and they named it Evatar.1 The origin of the name is that an “avatar” is a virtual representation of human, and so a chip that represents a female, was aptly named Evatar. Organs-on-a-chip are not a new concept. However, the female reproductive system is incredibly complex. And there has never been a system like this before. Evatar has compartments that are designed to mimic a woman’s ovaries, fallopian tubes, uterus and cervix. Because the vast majority of hormones are metabolized by the liver, the chip also includes a “liver compartment” that affords researchers a bio-plausible glimpse into how the system works.
To integrate the five aforementioned tissues into a single system, the team harvested tissues from a patient undergoing surgery for other reasons and capitalized on microfluidic control of tissue interaction to make sure that the system truly mimicked the female reproductive tract. With administration of exogenous follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the researchers can induce ovulation on Day 14 and induce a 28-day menstrual cycle—all on a chip! That proves that pituitary hormones set the cadence of the reproductive cycle both in vivo and in a microfluidic environment.1
In oophorectomized mice, researchers including those from the Evatar group recently demonstrated that a bio-prosthetic ovary 3-D printed with gelatin could house and nurture ovarian tissue. The ovary, ultimately yielded follicle-containing eggs and performed like an endogenous ovary.2 Prosthetic ovaries were transplanted into the mice and shown to not only engraft but also to fully restore menstrual regulation and function.
You may now be wondering how these technologies might change your practice as an ob/gyn. Well, creation of a bio-similar human-specific organ system is definitely going to accelerate ovarian stimulation research. With an advance like Evatar, it may be possible to take an ovarian biopsy from a patient and test her response to ovarian stimulation protocols before ever putting her through an entire in vitro fertilization cycle. An ovary-on-a-chip may also allow women who have had ovarian tissue removed for fertility preservation to have their oocytes cultured and harvested without requiring transplantation. Or, the system may simply help oncologists better understand the deleterious effects of chemotherapy on the female reproductive tract and move the field of oncofertility forward. And a prosthetic ovary may allow young cancer survivors who lack a successful graft of their own ovarian tissues to have normal reproductive lifespans.
Taken together, 2017 is an incredibly exciting time for reproductive biotechnology that is going to greatly improve how we care for patients.
1. Xiao S et al. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat Commun. 2017 Mar 28;8:14584.
2. Laronda MM et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun. 2017 May 16;8:15261.