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Introduction: The scope and incidents of environmental factors influencing the outcome of IVF are numerous and complex. However, we have attempted to present the reasons for modernizing Assisted Reproduction Technology laboratories in an accessible manner to the lay audience and as an introduction for the professional in the field.

How can a laboratory affect the chances of achieving a pregnancy in an Assisted Reproduction Technology (ART) laboratory?

Since the pioneering work of Drs. Edward and Steptoe culminated in the birth of Louise Brown, humans have been conceived and nurtured in laboratories. The amazing work of these pioneers resulted in the procedures know as in vitro fertilization (IVF). IVF is one option for infertile couples desiring to start a family. Since 1978 our knowledge has grown exponentially. There are now over 1,000,000 plus babies conceived through this process.

The drugs used to promote egg production have improved, as have the techniques of transferring embryos back into mothers. The systems used to culture the embryos have also advanced markedly. Today we can culture the embryos for 5 days allowing for improved embryo selection leading to higher pregnancy rates. However, the next aspect receiving attention is the environment of the ART laboratory. Laboratories that are poorly designed and maintained can lead to low rates of pregnancy due to embryotoxic materials in the environment.

The laboratory where embryos are cultured must provide the protective mechanisms the mother does naturally. Mother and her body provide the ideal place to conceive and promote the embryo’s development. Laboratories that are advanced have engineering systems to eliminate potential poisons before they can damage the growing embryo. These state of the art laboratories have robust systems to protect the developing embryo for air pollution and microbes. Failure to isolate the sensitive embryo from these materials can lead to higher levels of stress on the developing embryo. In some cases, the embryo’s ability to implant into the mother’s uterus is so compromised that no pregnancy is achieved.

How does nature protect an embryo?

Conception and embryo development is a complex event where the genes of the fertilized egg are activated and cell growth begins. This highly complex process is secured by the mother’s internal systems. The mother’s lungs provide air and remove wastes, her liver can detoxify toxic environmental contaminants. Her kidneys continually filter the blood surrounding the embryo removing wastes and poisons. The sum of these systems protects the embryo for environmental insults. The typical ART laboratory where in vitro fertilization is done lacks these wondrous facilities. Most laboratories have only a simple high efficiency particle elimination filter or HEPE to eliminate small particles that could be bacteria or mold. These HEPE membranes cannot stop the very much smaller molecules of environmental pollutants.

IVF procedures are done under sterile conditions so they should be safe. Right?

Sterility is a requirement and sterile techniques are used in all ART practices. Bacteria and other germs are just some of the hazards faced by an embryo developing outside the sheltering environment of a mother.

In modern laboratories, bacteria and germs are kept out by sterile techniques and the functional particulate filter but there is more. They have specialized chemical filters which trap environmental toxins thousands of times smaller than bacteria. These specialized filters remove air pollutants that can kill a couples’ hopes for a family.

ART laboratories designed with Alpha Environmental, Inc have rigorous construction standards that keep pollutants out of the laboratory and incubators where a couples’ hope matures into a healthy embryo. These laboratories use specialized building materials and construction techniques so that they are isolated from the outside world by physical barriers and a high level of pressurization.

A crude analogy could be made to the production of integrated circuits. These bits of wizardry are produced in factories with specialized environments that prevent particle contamination in the fabrication process. Chemical contaminants are also controlled in the clean rooms of chip fabricators. Modern laboratories do the same for gametes and embryos.

So, in summary, mother’s unique capabilities must be realized in the laboratory where an embryo grows.

But aren’t doctors offices and medical laboratories clean and is this environmental hysteria?

Medical offices and laboratories are clean to our senses but in many respects they are not clean enough. The modern medical office uses a bewildering number and quantity of toxic materials. Before the reader wonders why, please reflect on the need to kill germs in these facilities. Killing germs takes material that is effective in severely upsetting the process of the germ’s biochemistry. These same agents can also kill the far more sensitive human embryos were are culturing. So the chemical we must use to protect against infection can also kill the embryos. Please recall how mothers are urged to avoid smoking, ingestion of alcohol and avoid other hazards. These precautions are obvious to anyone. But the place where most embryos are grown can’t even approach her level of protection. We cannot match a mother’s wonderful capacity to protect. We must have a clean laboratory where these agents are prevented from entering into the laboratory.

This sounds reasonable but do we have data on what a typical IVF facility is like and is it as bad as depicted?

Dr. Jacques Cohen, a leading embryologist, has published numerous peer reviewed articles in such scholarly journals as Human Reproduction and Fertility and Sterility. The table below is an example:

Location

Range of Volatile Organic Compound’s

µg/m3

Outside Air

128-1,830

Air Supply

303-2,797

IVF Lab

310-4,404

Incubator

717-9,485

Adjacent to the IVF Lab

473-7,141

The table above shows the total level of pollutants found in several typical IVF laboratories. The striking fact is that the outside environment is actually cleaner in terms of pollutants than the laboratory where gametes and embryos are grown. The methods of analysis are those used by the US EPA as part of their programs to monitor airborne toxics.

Can you tell us more about these potential threats?

The ability to achieve a pregnancy is a multi-factorial process where maternal and paternal age and health status are major factors. But airborne toxins can come from outside the laboratory from air pollution, fires and construction activity. The toxins can come from the materials used in the laboratory. For example, the most common material for making cabinets and millwork can release formaldehyde. Formaldehyde is a known human carcinogen and mutagen. Its release from building materials is so well known that the levels in mobile homes are closely regulated by the U.S. government. Mobile homes make extensive use of particle board resulting in high levels of this irritant. Lest we paint too sensational of a picture, consider the real documented complaints of persons living in FEMA trailers after natural disasters.

Below is a picture of a mouse embryo. The mouse is used as a test subject to monitor the IVF process. These mouse embryo assays are used to gauge the suitability of products in the laboratory. The two cell embryo below is typical of the beginning of the assay.

After 3-4 days it will develop into a blastocysts, the stage we want to reach before transferring the healthy growing embryo into the recipient mother. The result is a clean environment that will look like this.

However, exposure to formaldehyde results in cellular breakdown and lyses as depicted below.

Proper laboratory design and construction can prevent this insult and degradation of a couple’s hopes and dreams.

How can these threats to reproductive success be eliminated?

By analogy to the clean rooms, in the semiconductor we utilize biological clean rooms where microbes and pollutants are eliminated. Several researchers, including Dr. William Boone and Dr. Kathy Worilow, have described the positive effects of these specialized facilities.

How do laboratories designed under Alpha Environmental, Inc guidelines stack up compared to the pollution levels around them?

Laboratories designed to our guidelines are tested to confirm they are functional in reducing the load of pollutants that embryos must face. The table below summarizes the differences between the pollution load and the levels inside the IVF laboratory.

Lab #

Outside or

 Pre-filter

VOC μg/m3

Post-filter or

IVF Lab

VOC μg/m3

1

12,014

227

2

286

141

3

447

402

4

597

387

5

10,711

701

6

4,199

614

7

57,670

606

8

647

298

9

113

126

10

2,462

369

11

134

101

Mean of all Modern IVF Labs

7,513

322


 


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