A reproductive physiologist working in an in-vitro fertilization clinic in 1999 noticed that her patients’ pregnancy rates were dipping up and down, for no discernible reason.

Dr. Kathryn Worrilow and her colleagues at Lehigh Valley Hospital-Muhlenberg decided to figure it out. They examined the incubators, they looked at their lab protocols, they explored other possible causes — nothing.

Then she left work one night and noticed that the helipad was being resurfaced, and a light bulb went off.

“The last thing we looked at was the air,” Worrilow told The Morning Call, about her team’s search for the cause in the up-and-down fertility rates. “Because we ran a cleanroom. Why would you look at the air?”

Dr. Worrilow obtained documentation about the asphalt being used on the helipad and discovered a common chemical that’s a pathogen to embryos. Human embryos don’t have a mechanism for defense against biological contaminants. Low levels of the same chemical were later discovered in the IVF lab. Other environmental factors from outside the hospital — road resurfacing, car exhaust, etc. — were bypassing the ISO 5/Class 100 facility’s air purification system. 

Worrilow went on to found LifeAire; she holds two patents for an air-filtration system which filters out the contaminants that can affect embryos. The system is already utilized by several IVF programs around the country, and Worrilow is in talks with other hospitals to use it for non-IVF applications: preventing secondary infections, protection in compounding in pharmacies, NICU and PICU patient protection, long-term care for seniors, operating rooms, and burn units.

Air quality is an important factor in the success of IVF. VOCs and microbes are harmful to embryo development in vitro, along with other factors such as temperature and light. One study shows that ambient air quality could affect gamete and embryo quality at critical times when either are outside the controlled environment of the incubator. Fertilization rates, number of transferable embryos, and initial pregnancy rates were observed before and after the implementation of an IVF lab, retrieval room, and transfer room; the rooms were outfitted with an increased number of fresh air exchanges and positive pressure throughout. The experiment also considered the avoided use of building materials that release VOCs and both chemical and particulate filtration of outside air.  

Another study shows that IVF labs need to utilize HEPA filers and activated carbon filters plus positive pressure for air particulate control, with or without CODA system. 

A 1999 study determined that a Class 100 cleanroom — along with an anteroom and an adjacent operating room — improved both air quality and IVF rate, and the new clean facilities helped increase the number of embryos past the four-cell stage available for transfer. Clinical pregnancy rates decreased from 35 percent in 1993 to 16 percent in 1994, when numerous construction odors were detected. Following the cleanroom construction, rates from 1995 to 1997 climbed to 20 percent, 32 percent, and 59 percent, respectively. 

Air quality can also affect pregnancies before conception or egg/sperm retrieval. A 2005 study found that exposure to intermittent air pollution can result in sperm DNA damage, which increases the rates of male-mediated infertility, miscarriage, and other adverse reproductive outcomes. Maternal exposure to poor air quality also affects a pregnancy in a negative way.

Improving the quality of embryos may also lead to a lower selective reduction rate. Selective reduction is a procedure that reduces the number of fetuses in a multiple pregnancy. Multi-fetal pregnancies carry increased risks when compared to singleton pregnancies — gestational diabetes, the chance of a C-section, the chance of premature birth, birth defects, and miscarriage of one or more of the fetuses. One study found that a first trimester reduction of twin pregnancy to a singleton pregnancy significantly lowers the risks of twin pregnancy and improves obstetrical outcome. Reductions performed beyond 15 weeks gestation saw a higher proportion of pregnancies with at least one major complication (examples: preterm delivery, IUGR, placenta abruption, PPROM).
 

CONFERENCE AGENDA ANNOUNCED:

The highly-anticipated educational tracks for the 2015 R&D 100 Awards & Technology Conference feature 28 sessions, plus keynote speakers Dean Kamen and Oak Ridge National Laboratory Director Thom Mason. Learn more.

Fertility treatments have caused a significant increase in multi-fetal pregnancies. According to the American Congress of Obstetricians and Gynecologists (ACOG), multi-fetal pregnancies increase both maternal and neonatal morbidity and mortality; high-order multi-fetal pregnancies present higher risks than do twin pregnancies. A woman undertaking IVF treatments has a 22-fold increased risk of conceiving twins, and a 100-fold increased risk of conceiving triplets, when compared with natural conception. Infants resulting from a multiple pregnancy are at increased risk of prematurity, cerebral palsy, learning disabilities, slow language development, behavioral difficulties, chronic lung disease, developmental delay, and death. 

Selective reduction carries many moral/ethical dilemmas along with it. Research is being done to determine how to avoid situations where selective reduction needs to be considered.

Dr. Brandon Bankowski, a partner at Oregon Reproductive Medicine in Portland, Ore., says that his company is looking to lower the selective reduction rate by improving the science behind the embryos.

“Our goal is to get to the point where we transfer one embryo and we have one baby,” Bankowski told Oregon Public Broadcasting. “The only options that we offer to our patients now are transferring one or two embryos. We would never transfer more than that.”

Donor eggs are frozen and collected in a cleanroom at ORM. Bankowski says that the company worked with cleanroom engineers at Intel to develop the facility. Those who enter the cleanroom are instructed not to wear perfume, which contains volatile organic compounds (VOCs) that could harm developing eggs.

In ORM’s latest process, they take a small slice off the outside of a developing embryo and place it on a microchip, which contains a series of sensors that detect if a specific gene is corrupted.

In the past, about 10 genetic probes were attached — today it’s about 500,000.