Part I: A brief description of the Early Life Issues

2. What are New Reproductive Technologies?

New Reproductive Technologies (NRT) refer to any artificial intervention employed to obtain a living human being at any stage of development for “reproductive” purposes. That is, any method of making a human being in the embryonic stage of life by any means other than sexual intercourse.

Cloning is included in these because a human being is created and is fully in existence from the first moment of the proper ordering of the genetic material that makes up the human being at the earliest stage of life whether that ordering has been brought about by the combination of oocytes and sperm or by any other non-sexual method. A cloned human being is fully a human being at the earliest stage of his life.

Because of the size and complexity of the subject, however, cloning is treated in a separate section in this text.

A variety of techniques

Currently, techniques in use in fertility treatment facilities include:

· fertility enhancement drugs

· artificial insemination (AI)

· in vitro fertilization (IVF)

· intracytoplasmic sperm injection (ICSI)

· pre-implantation genetic diagnosis (PGD)

• zygote intrafallopian transfer (ZIFT)
• gamete intrafallopian transfer (GIFT)
• assisted hatching
• twinning or blastomere separation
• surrogacy
• embryo “adoption”
• gamete donation

Recent experimental advances include the creation of embryos from sperm or oocytes only; the creation of embryos using combinations of human and animal DNA; the development of artificial wombs; and the creation of genetically matched embryos to be used as tissue donors for siblings or other relatives with serious illnesses.

Fertility Enhancement Drugs

Synthetic hormonal agents that stimulate ovarian follicle[1] development are often tried first in cases where infertility is the result of anovulation. These drugs fall into two categories: clomiphene citrate (commonly called Clomid or Serophene), given in pill form; and the injectible Gonadotropins (sold as Humegon, Pergonal, Repronex, Fertinex, Follistim and Gonal-F.)

Clomiphene citrate works by "tricking" the system into thinking there is insufficient estrogen and indirectly stimulating the ovaries. Gonadotropins contain follicle stimulating hormone (FSH) and directly stimulate the ovaries.

Fertility drugs are often associated with the increased incidence of multiple births. In one famous case in the UK, a woman using them found that she was pregnant with seven children at once. In such cases, it is common for doctors to select and abort one or more of the children, in a procedure referred to as “selective reduction” or “foetal reduction”.

Artificial Insemination (AI)

AI is typically recommended as the first stop for the treatment of infertility due to:

• mild to moderate male factor infertility
• "unexplained" infertility
• cervical mucus insufficiency
• hostile cervical mucus
• various structural abnormalities in the woman

AI involves injecting a sample of specially treated sperm from the male partner, or a third party donor, into the female partner's reproductive tract. The sperm sample is obtained through masturbation. If the sperm is obtained from a donor, the resulting child will be the biological offspring of the woman and the donor, not the woman and her husband or chosen partner.

Different types of AI include:

• intracervical (in the cervical canal)
• intrauterine (in the uterine cavity)
• intrafollicular (in the ovarian follicle)
• intratubal (in the fallopian tubes).

When AI and/or fertility drugs fail, couples who can afford it often move to the more dangerous and invasive and expensive in vitro fertilization techniques.

In vitro Fertilization (IVF)

The term ‘in vitro’ is simply Latin for “in glass” and refers to the method of creating a new human being at the earliest embryonic stage of life by physically mixing together human sperm and oocytes in a laboratory. The resulting embryos are implanted into the uterus of the patient or a surrogate and brought to term. Those embryos not selected for implantation can be stored cryogenically, donated for scientific research or destroyed.

The practice was developed in the 1970’s by Drs. Patrick Steptoe and Robert Edwards and was successfully employed for the first time in England with the birth, on July 25, 1978, of Louise Joy Brown who was hailed in the press as “the world’s first test-tube baby.” In fact, Louise Brown can more accurately be described as merely the first IVF baby to have been successfully brought to term.

The success rate for pregnancy with IVF is estimated by the best commercial clinics at about 15-25%, depending upon various factors such as the age of the woman. This means that it is common to have patients make several attempts, each costing thousands of dollars. In Canada, IVF treatments are not often covered by public health insurance plans and are laregly the province of private, for-profit clinics.

In normal IVF procedures, more embryos are created in each round of treatment than can be implanted at once and the so-called “spare” embryos are stored frozen in liquid nitrogen and can be thawed out and implanted for subsequent attempts.

The creation of multiple embryos enables several attempts with different embryos created in the same batch. It also enables the selection of embryos for various desired genetic traits and to “screen” for various potential medical problems such as Down’s syndrome or possible predispositions to heart disease or cancer. Preimplantation genetic diagnosis (PGD - see note below) by various methods is now normally offered as part of the IVF procedures in most clinics. Sex selection of embryos, though in some countries technically illegal, is also routinely offered as part of the program.

The IVF Procedure:

The procedure usually begins on the third day of menstruation and starts with a regimen hormonal drugs to stimulate the ovaries to begin producing oocytes at an accelerated rate. Typically approximately ten days of injections are required.

A procedure is then performed to retrieve the mature oocytes using an ultrasound-guided needle piercing the vaginal wall to reach the ovaries. The retrieval procedure takes about 20 minutes and is usually done under conscious sedation or general anaesthesia.

The oocytes are then examined for imperfections and those most likely to be fertilized are selected and mixed in a culture medim for about 18 hours. By that time fertilization should have taken place and the embryo would show two pronuclei[2].

They are left in the medium and allowed to develop to the 6-8 cell stage (about 48 hours.) In some cases the embryos are placed into an extended culture system until the blastocyst stage.

Intracytoplasmic sperm injection (ICSI)

A procedure in which a single sperm is selected and injected directly into a mature oocyte using a micropipette. This procedure is most commonly used to overcome male infertility problems. After the procedure, the oocyte is placed into cell culture and checked for signs of fertilization and division.

ICSI is one of the artificial procreation techniques most frequently cited in studies on the incidence of birth defects in NRT’s. Problems associated with ICSI include reduced testosterone levels in ICSI-conceived boys. Studies have shown a relationship between ICSI and infertility, cystic fibrosis, cancer, and developmental delays in children conceived by the method.

In March 2002, two major studies were published that found that babies conceived as a result of ICSI were twice as likely to suffer severe birth defects. The authors of one of the studies, published in the New England Journal of Medicine, concluded,

“As compared with natural conception, the odds ratio for a major birth defect by one year of age, after adjustment for maternal age and parity, the sex of the infant, and correlation between siblings, was 2.0 with intracytoplasmic sperm injection, and 2.0 with in vitro fertilization…

“Infants conceived with use of intracytoplasmic sperm injection or in vitro fertilization have twice as high a risk of a major birth defect as naturally conceived infants.”

Preimplantation Genetic Diagnosis (PGD)

Many IVF facilities offer preimplantation genetic diagnosis, a procedure that is under development but is meant to detect possible abnormalities. It also detects possible genetic problems or genetic predispositions to future illnesses like cancer or heart disease. Those embryos not selected are normally either destroyed or donated for research.

In the procedure, a single blastomere is removed from the embryo after the trophoblast has formed. This is examined for genetic abnormalities. The removal of the blastomere from the days-old embryo can in some cases cause damage to the embryo.

Most IVF facilities include PGD as a normal service associated with fertility treatments and many hospitals will include “genetic counsellors” who may advise patients, based on a diagnosis of a genetic abnormality or possible inherited traits, to abort a child.

Gamete intrafallopian transfer (GIFT)

GIFT is used in instances where the fertility problem relates to sperm dysfunction, and where the couple has infertility from an unknown cause. Some patients may prefer the procedure to IVF for what are considered “ethical reasons”, since the fertilization takes place inside the body.

Fertility drugs are administered to the woman to stimulate ovarian follicles. When the follicles are mature, the woman is injected with Human Chorionic Gonadotropin (HCG). The oocytes are harvested approximately 36 hours later, mixed with sperm and the resulting zygote is placed in the woman's fallopian tubes using a laparoscope[3].

Zygote intrafallopian transfer (ZIFT)

ZIFT is used in cases where infertility is caused by a blockage in the fallopian tubes. Oocytes are retrieved from the ovaries and fertilized in the lab. The resulting zygote is then placed into the fallopian tube by the use of laparoscopy. The procedure is a spin-off of the gamete intrafallopian transfer (GIFT) procedure.

Assisted hatching

In the first stages of development, the embryo is surrounded by a strong membrane (made of glycoproteins) called the zona pellucida. Expansion of the embryo as it develops and grows, together with the production of enzymes causes the zona pellucida to open, releasing the embryo. This is called “hatching.” The embryonic cells then come in contact with the lining of the uterus, allowing implantation.

In some cases, the zona does not break down properly and a procedure, assisted hatching, is performed. Performed under a microscope assisted hatching involves holding an embryo with a pipette, and, using a fine needle filled with a hatching solution, a hole is drilled in the zona. The embryos are then transferred to the woman’s uterus. Because there is now a hole in the zona, the embryo is more exposed to the environment and at risk of bacterial infection.

Blastomere separation or “Twinning”

Propagation of embryos by “twinning,” or the separation of a blastomere from an early-stage embryo is a form of asexual reproduction and therefore is classed as cloning.

This procedure is common in animal husbandry and has been used in veterinary medicine for some years. The removal of blastomeres from a very early stage embryo does not always result in the death of the embryo but the risk of damage in any micromanipulation is high.

In blastomere separation a zygote created in vitro is allowed to divide until it forms a mass of about four cells. The outer membrane is removed and it is placed in a solution that causes the blastomeres to separate. Each blastomere is placed in culture where it forms an embryo containing the same genetic makeup as the original embryo, an identical monozygotic twin.

The cells in the inner cell mass of the blastocyst are also totipotent and can be induced upon removing them from the embryo to begin dividing as separate embryos. There are two methods of artificial twinning in use. In one, the most common, blastomeres are removed from the embryo and induced to begin division as separate embryos. In the other the entire embryo, including trophoblast, is split and the two parts induced to form two separate embryos.

Unlike the more difficult methods of cloning such as somatic cell nuclear transfer (SCNT), embryos formed by blastomere separation and blastocyst splitting include both the nuclear DNA and the mitochondrial DNA outside the nucleus of the original zygote. Both kinds of “twinning” are advertised by IVF centers as a means of “embryo multiplication” - which could not only reproduce new embryos for infertility but also for pure research purposes only.

Surrogacy

A surrogate mother is also called a “gestational carrier.” Surrogacy is an arrangement whereby a woman agrees, either for monetary consideration or not, to become pregnant for the purpose of gestating and giving birth to a child for others to raise. She may be the child's genetic mother or she may be implanted with someone else's embryo (called gestational surrogacy).

Embryo adoption

IVF typically results in more embryos than can be carried to term by the clients. Unused embryos, often refered to in the press as “spare”, are often stored cryogenically, sometimes indefinitely. In some cases, the extra embryos are given, or sometimes sold, to other couples or women for implantation.

Legal cases are starting to become common in cases of embryo adoption and surrogacy over the “ownership” of embryos.

Pro-life ethicists are divided on the subject with some saying that once the embryo is created, adoption gives the best possible chance of life. Others argue that the implantation procedure is itself illicit and that such embryos ought to be allowed to die naturally, according to the same ethical criteria as individuals dependent upon life support machines.

Gamete donation

Donation of oocytes or sperm has become a mainstay of the IVF industry. Most NRT facilities keep a stock of gametes from donors to use in cases where infertility is caused by the clients’ own biological insufficiency.

To donate sperm a man must usually be screened medically to meet specific requirements regarding age and medical history. A man generally donates sperm at a clinic by way of masturbation. Most establishments at which sperm is donated stock pornography to assist the donor in reaching orgasm.

Donated gametes have had an enormous impact on family law. In countries where IVF is common, laws are starting accept other categories of parenthood, especially in custody cases. A child conceived through donated gametes can have both “genetic” and “social” parents. A child conceived in this way and implanted in a surrogate mother can, in law if not in biological reality, have a genetic and a “social” father, a genetic, gestational or surrogate mother and a social mother. Theoretically a child thus could have 5 parents.

Other concerns with gamete donation surround privacy laws. In Canada, when legislation was being considered, some MP’s brought up the issue of donated gametes and the problem of assuring that a child knows his parentage. Sperm is normally donated anonymously, raising concerns of increasing the risk that rare recessive disease causing genes will become common in the population. Concerns were also voiced of unwitting consanguinity in marriage for the child concieved by donated sperm. One man in a posting on a website called the DonorSiblingRegistry.com claimed to have fathered at least 650 children via sperm donation.

This danger prompted Sweden, Norway, the Netherlands, Britain, Switzerland, Australia and New Zealand to disallow anonymous sperm donation. Canada and the US have no such limitation.

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[1] Ovarian follicles are the roughly spherical aggregations of cells found in the ovary. containing a single oocyte. These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single competent oocyte.

[2] Pronucleus is the haploid nucleus of a sperm or oocyte after fertilisation but before fusion of the nuclei.

[3] Laproscopy is also called minimally invasive surgery (MIS), band aid surgery, keyhole surgery, or pinhole surgery. It is a surgical technique in which operations are performed through small incisions (usually 0.5 - 1.5 cm) as compared to larger incisions needed in traditional surgical procedures. It involves the use of a laparoscope, a telescopic rod and lens system that is usually connected to a video camera.