Confessions of a Birth-a-holic

Group Introduction

 * Group Number: 05
 * Group Members: Irene So, Wendy Chiu, Eileen Chhom, Jennifer Lieu
 * Lecture: CPSC 203 WI09 L04 Donny Cheung
 * Tutorial: T22 Fahim Zibran

Technology & Argument
Technology: In vitro Fertilization Topic of Discussion: The abuse of the technology for reasons beyond infertility Issue: With the recent headlines surrounding fertility treatments, our group decided to tackle the social and ethical issues surrounding the new technology. Though it provides hope for couples who want to conceive children, there are many ethical concerns surrounding the process as in the case of the “Octomom,” who recently gave birth to a set of octuplets, or to the 60 year old woman who gave birth to a set of twins. In both cases, in vitro fertilization was used to conceive the children. Our group will explore the pros and cons to the controversial treatment.

What is IVF?
One of the biggest controversies we face in our growing society today is the idea of birth through the tools of in vitro fertilization. In vitro fertilization (IVF) defined as; a specialized technique, by which an ovum, esp. a human one, is fertilized by sperm outside the body, with the resulting embryo later implanted in the uterus for gestation, is becoming a growing phenomenon between couples who are unable to conceive due to various complications. For starters, infertility ranks number one on the list of problems which highly results in couples resorting to IVF. In vitro fertilization began as a work in progress originating in England dating back as early as the 1800’s. Only later was it found to be a success in 1978 under the works of Dr. Edwards, an embryologist and Dr. Steptoe, a gynaecologist. Since then the technology surrounding IVF has improved greatly crediting in over 20 000 births. With curiosity, determination and decades of technological advances the miracle of life along with all its complications can be set right in front of you viewed in what scientists refer to as a Petri Dish.

History
On July 25, 1978, Louise Joy Brown became the first baby in the world to be born through in vitro fertilization. The mother was unable to conceive so under the advice of gynecologist Dr. Patrick Steptoe, she underwent a laparoscopy. The doctors extracted a single mature egg from one of her ovaries and combined it with her husband’s sperm. After the cells began to divide into an embryo, it was placed into the uterus for a natural birth.

However, the first case of in vitro fertilization dated back in 1891, where the process was inclusive to animals, mainly rabbits. Walter Heape reported the first case of embryo transplant when he worked with two species of rabbits—Angora and Belgian. In the Angora species, he removed its embryos from the oviducts and placed them into the uterus of an already impregnated Belgian rabbit. The experiment resulted in the Belgian rabbit giving birth to four Belgian breeds and two Angoras. This proved that it was possible to transfer and plant embryos into a carrier without affecting the development of the offspring or the carrier.

The developments led Gregory Pincus, along with many other scientists to further study the effects of embryonic transfers. He reported that human eggs would mature within 12 hours of being released from the follicles of the ovaries if harvested in a lab. However, the results were later rejected when Physiologist Robert Edwards exercised the procedure and concluded that human eggs could not be matured in labs. Instead, it took twice as long for an egg to mature as reported and that it must occur in the ovaries just before ovulation occurs.

In late 1968, Edwards worked with Steptoe after discoveries were made with laparoscopy. The procedure required that the egg be removed from the follicle using the new technology and fertilized in the lab before it was placed back into the uterus. The sperm had to undergo capacitation—changes in the plasma membrane, for the egg to fertilize. This required that the egg was matured before removal so hormonal injections of progesterone were required.

In 1976, a report was published between Edwards and Steptoe that announced a clinical pregnancy when an embryo was transferred into the uterus at a sixty-four cell division stage in the embryonic development. Unfortunately, it resulted in a tubual ectopic pregnancy and had to be removed. They both then decided it was best to implant the embryo once it had reached the eight cell division stage and with no hormonal injections. On their second attempt, Louise Brown was conceived.

Process
Multiple tests are required to determine whether the couple is eligible for IVF. Some tests include blood tests, STD tests and mammograms. If the test results are satisfactory, then the couple is allowed to proceed with the IVF process. They must sign a consent form so that they are aware of the terms and conditions of this process and to allow the clinic to start the process. Step 1: Super Ovulation A woman’s body functions only to develop one egg (oocyte) fully during every menstruation cycle she undergoes. In super ovulation, injections and medications are given to the woman to stimulate the ovaries to produce more than one egg at a time. The purpose of developing more than one egg at a time is to increase the success rate of conception. The injections and medications help the woman’s body to prepare several eggs until they are suitable to be extracted. This disrupts the natural cycle of a woman’s body by increasing and suppressing certain hormones. Hence, there will be side effects and possibly severe risks that will require hospitalization. As the eggs begin to develop inside the follicle cells (cells that nourish the egg), ultrasounds and blood tests will be performed. Clinicians monitor the growth of the follicle cells closely until they are ready. Step 2: Extracting the Oocytes The woman will have an intravenous catheter connected to her and will be given pain medication if needed just before retrieving the eggs. As well, the woman will monitored for her pulse, heartbeat, pressure so that she is in a suitable condition before and during the process. Her labia and vagina will be cleansed with a special solution. Then, an ultrasound probe along with a needle will be inserted though the vaginal walls and into the ovaries. The ultrasound performs as a guide to locate where the follicle cells containing the eggs are. Once, the clinician has located the follicle cells, the follicular fluid will be extracted and be stored in a test tube. This process takes about 20 minutes to complete. Step 3: Collecting the Sperm On the same day, when the woman is having her eggs retrieved, the man will need to prepare a sample of his semen usually by masturbating. The man may feel pressured or stressed to provide a sample on the spot at the clinic. In this case, he may have a sample beforehand and have the specimen frozen in the lab. Another alternative for the man is to undergo testicular biopsy where the sperms can be collected. Step 4: Insemination Once both the eggs and sperms are retrieved, it is immediately taken to the laboratory for insemination. Insemination refers to the process where the egg is fertilized by a sperm manually and not by sexual intercourse. The eggs and the sperms are in a special nutrient medium where they are combined. It is recommended that all eggs extracted to be inseminated as this will increase the chance of developing an embryo. Under specific conditions, the egg along with the sperm will be incubated overnight. Following, a laboratory technician will examine whether or not the eggs have been fertilized properly. If not, the technician will repeat the process of insemination. However, if proper fertilization fails again, the IVF process will be cancelled. Once the technician determines which embryos are the healthiest(usually day 5 also known as the blastocyst stage), they will be transferred to the woman’s uterus. Step 5: Transferring the Embryo The woman will have a catheter being inserted in her so that the embryos can be implanted on the uterus after. The embryos are placed into the catheter which will pass through the cervix and reach the top of the uterus. After finding the correct location, the clinician will make sure that all embryos are placed onto the uterus. Usually 2-4 healthiest embryos are chosen to be placed. When the procedure is finished, the woman is able to return to her daily routines. Step 6: Follow Up After the embryos are placed, the woman will need to take medications to prepare the body for a possible pregnancy. It will take some time for the embryo to implant itself into the uterus and start the process of pregnancy. About 12-14 days later, the woman will have to go back to the clinic and do a pregnancy test. If the pregnancy test shows up as positive, the IVF has been successful and now the couples will be on their way waiting for their baby. However, if the pregnancy test is negative, then the couple may want to use the remaining embryos to repeat the procedure or find alternate ways of conceiving.

Predictive Measures
- FSH levels of the cycle on day 3 are predictive of pregnancy outcome and stimulation characteristics in IVF, and may be useful in counselling patients. - the number of small follicles present prior to ovarian stimulation better predicts the outcome of IVF than ovarian volume or age alone; those with inactive ovaries will poorly respond to IVF treatment, which is important for counselling couples and optimizing resources

Advantages & Disadvantages
Advantages: There are three main benefits of IVF. No sexual intercourse is necessary to conceive-- the treatment acts as an assisted reproductive technique because insemination is performed through laboratory procedures. Also, it is a very beneficial treatment for those who have been trying to conceive or are infertile (either partner). As well, IVF can be beneficial to couples that suffer from genetic disorders. Through the selection of certain embryos, tests can be done to ensure it is healthy and free of genetic disorders before insemination occurs.

Disadvantages: There are many methods of determining and ensuring a successful implantation, but even then, there are many risks and disadvantages associated with this type of treatment.

The three main disadvantages or risks of IVF are:

- multiple births (as shown in the picture to the right)

- birth defects (Prevalence of Major Birth Defects Diagnosed by One Year of Age)

- birth defects caused by multiple births(The Adjusted and Unadjusted Relative Risk of 42 CDC Reportable Birth Defects and 8 Major Birth Defects Classification by Plurality (Florida, 1996-2000))

Success Rates
Success rates of IVF heavily depend on the age of the woman. The older the woman is, the less likely that IVF will succeed. Women under the age of 35 success rate is 30-35% Women ages 35 to 37 success rate is 25% Women ages 38 to 40 success rate is 15-20% Women ages 40 and above success rate is 6-10% Note: All these percentages are approximations. It can vary due to the women’s body ability to adapt to her pregnancy or previous medical conditions that may prevent pregnancy. A success rater for in vitro fertilization does not mean the same thing as a success birth rate since the woman may experience a miscarriage after a successful in vitro fertilization process.

Costs Associated with IVF
There has been an incredible amount of debate on who should be allowed this procedure and whether insurance policies or other methods of funding/coverage should be allowed and to whom. IVF is a costly procedure for most couples and most insurance companies do not provide coverage for this. There are various plans that couples can choose when deciding to proceed with IVF. Some are definitely more expensive than others.

From the first to sixth cycle of IVF, the cost increases, on average, from $66,667 to $114,286. The cost increases because with each cycle of failed fertilization, the probability of successful subsequent efforts decreases. The cost per delivery ranges from $44,000 to $211,940. Patients who have a better chance of successful IVF through various diagnosis or methods are expected to pay about $50,000 per delivery for the first cycle and $72,727 for the sixth cycle. The numbers drastically increase to $160,000 for the first cycle and $800,000 for the sixth cycle for couples containing an older woman and a diagnosis of male-factor infertility in the male.

In Canada, there are some conditions in which the IVF procedure would be funded such as the woman having both her fallopian tubes blocked. Also, ultrasound scans, medications, donor eggs/sperm, and laboratory charges are several factors that can affect the costs. Hence, it is very important that you contact the clinic for information because costs can be subjected to change.

Money Back Guarantee Program

“The Center for Reproductive Health (CRH) is now offering a service called the IntegraMed Shared Risk Refund Program. For one fee (excluding the cost of medications), women may attempt up to three fresh IVF cycles and three frozen embryo transfer cycles. If the patient doesn’t take home a baby, 70 percent of the fee is returned (100 percent if donor eggs are used).

Fees for IVF programs vary across the country, but the cost of one fresh and one frozen IVF cycle at the CRH is $7,800 (without medications). The Shared Risk Refund Program costs less than two cycles at the CRH for eligible patients.

Assisted Hatching
Assisted Hatching: Because the zona may be abnormally thick in some cases, assisted hatching enables part of the membrane to be chemically thinned through a micromanipulation technique on the third day of the development of the embryo.

This method is specifically recommended for patients who either: - are over the age of 37 years - have a reduced ovarian reserve (determined by a day-3 FSH level) or - have lower antral follicle counts

Also, those who do not respond well to gonadotropin stimulation or experienced previous failure in implantation may consider this alternative.

Cryopreservation
This technique of freezing the embryo with liquid nitrogen is an alternative for those who have an excess of normally-fertilized embryos or blastocysts of high quality remaining after embryo transfer.

The embryos are frozen at either the zygote stage a day after egg retrieval or on day 5-6 of the blastocyst stage. They can be store for several years below subzero temperatures and can be thawed and transferred to patients in a frozen embryo transfer cycle.

Preimplantation Genetic Diagnosis (PGD)
Performed in union with IVF, it is used for detection of genetic abnormalities in embryos, such as aneupoloidies (an extra or missing chromosome), prior to implantation to avoid transferring affected embryos. There are more than 50 types of single-gene mutations that are diagnosable today.

The first step is perform an embryo biopsy, which is taking a single cell from an embryo with 5 or more cells on day 3 of development. The biopsied cell is lysed, placed on a glass slide to expose it to the nuclear material and examined through Fluorescence In Situ Hybridization (FISH) analysis to detect abnormalities in the chromosomes. However, if the cells need to be analyzed for single-gene mutations, they must be transferred to tubes in lysis buffer and it is then examined through polymerase chain reaction (PCR) analysis. Results are presented on the fifth day after the egg is retrieved and the embryos that are considered normal will be transferred.

This method is specifically recommended for patients who either: - have had experiences of recurrent miscarriages/failed IVF attempts, despite having high-grade embryos - at an advanced maternal age (38 years and over) - have unexplained infertility or - have severe male factor infertility or inherited genetic disorders, such as cystic fibrosis, Tay Sachs disease, and Myotonic dystrophy

The risks associated with this process is quite minimal, compared to the benefits. There is usually a 10% misdiagnosis rate due to mosaicism, a condition in which a cell of a multicellular embryo is genetically different than the other cells.

Issues
Ethical Concern: The most recent and controversial issue regarding the abuse of IVF treatments involves a woman named Nadya Suleman, also infamously known as “Octomom”, who underwent IVF treatments and experienced a multiple birth of eight. She already previously had four single births and one fraternal-twin birth through IVF treatments as well.

As mentioned earlier, multiple births is highly dangerous and can pose serious risks to the babies, as well as the mother.

"You have the right to as many children as you desire," said Reproductive Specialist Dr. Claudio Benadiva. "But not at one time; not all together, that's where our responsibility comes into the picture."

The controversy lies on whether the doctor providing the treatments should be held responsible or the mother of eight, and the ethical concerns revolving around the woman’s obsession with the expensive treatments. Many place the responsibility on the doctors, acknowledging Nadya’s previous IVF treatments and deeming her unable to make logical decisions regarding further IVF treatments, especially involving the transfer of multiple embryos.

"When you look at the national data, the percentage of pregnancies that result in multiple pregnancies, has been dropping year after year," said Dr. Benadiva. "Our society has established guidelines."

This case has now triggered the creation of bill SB 647 by Senator Gloria Negrete McLeod, placing fertility clinics and cosmetic surgery providers the jurisdiction of the Medical Board of California. Bill SB 169 has also been introduced in Georgia by Senator Ralph Hudgens to provide oversight of the fertility industry.

"For 30 years now, assisted reproduction has develop not just into a powerful technology in new ways of creating babies, but a $3 billion business that in the us is essentially free of oversight," said Jesse Reynolds, spokesman for the Center for Genetics and Society."

Multiple gestations, having two or more fetuses in the uterus at the same time, occur very rarely in natural pregnancies. Twins are the most common higher order multiples and triplets, quadruplets, etc. seldomly occur. However, due to the availability of infertility treatments, higher order multiples occur much more often and are often very dangerous to both the fetuses and the carrying mother. 80% of three or more higher order multiples were due to the successes of infertility treatments and are at a higher risk of birth complications.

The most common complication of multiple gestations are premature delivery, which can result in many more specific complications, such as respiratory distress syndrome and necrotizing enterocolitis, and low birth weights. These complications heavily contribute to the mortality of multiple gestations. According to U.S. Vital Statistics data, twins are about 7 times more likely to die during the first month, and 5 times more like to die during the first year, compared to single-born babies. Triplets are an astounding 20 times more likely to die during the first month, and 12 times more likely during the first year. Multiples are also 4-10 times more likely to experience cerebral palsy and permanent handicaps than single-born babies.

Carrying mothers are also at risk to mortality and massive health care costs. They also risk severe nausea and vomiting (hyperemesis gravidarum), bladder/kidney infections, iron deficiency anemia, hypertensive disorders and many other complications, including uterine ruptures, bleeding complications, and a high chance of Cesarean sections.

Multifetial pregnancy reduction (MFPR) can be considered if a high-order multiple gestation is conceived, which reduces the number of fetuses in a high-order multiple pregnancy of 3 or more to about 2, and increases the chances of the remaining fetuses of surviving. The "unwanted" fetuses are injected with a potassium chloride solution, which stops its heart. The fetus is then absorbed the by carrying mother's body.

On February 3rd, 2009, an infertile 60-year-old woman gave birth to twins through IVF treatments. They were delivered prematurely by Cesarean section; the mother was in intensive care and the twins were in neonatal intensive care.

This has spurred controversy and debate regarding the ethics of allowing IVF for a woman of her old age. "... we're stretching the boundaries and everything else -- but there's so much more involved in this. It's not just having the babies and being born. There's not just one generation gap here, there's two generation gaps. They're really what would be like the age of grandparents," says obstetrician Colin Birch.

The woman originally had three embryos but one had to be terminated and the remaining two that were born caused her to have high blood pressure and diabetes. She also had a condition called placenta previa, in which the placenta is attached to the bottom of the uterus and covers all or part of the cervix, possibly resulting in severe bleeding.

She experienced hemorrhaging so an emergency Cesarean section had to be made to deliver the twins. The bleeding was so severe that her uterus had to be taken out and she required multiple blood transfusions to recover her from the massive blood loss.

The maximum ages for the allowance of IVF treatments is between 45 to 50 years old in Canada. In other countries, the cutoff age for IVF treatments are very vague or relaxed. According to Glenys Godlovitch, many people, including this 60-year-old woman, seek IVF treatments elsewhere, in other countries, and come back to Canada for delivery, abusing the health-care system we have in Canada.

There have also been cases of women as old as 70 years giving birth through IVF treatments.

Women of an older age experience pregnancy complications even if they use eggs donated from healthy, younger women. They risk experiencing gestational diabetes, hypertension and intrauterine growth restriction. Older women also have a higher chance of the fetus dying or being born prematurely, possibly due to having a multiple pregnancy. It has also been noted in a study that the rate of C-sections is close to 100% in women who deliver in their mid to late forties.

Environmental Concern: It has been mentioned earlier that by transferring multiple embryos, the woman may result in giving multiple births. About 25% of all in vitro fertilization pregnancies were either twins or triplets. The issue of multiple births has led people to be concerned about being closer to overpopulating than ever before. As technology advances, success rates for in vitro fertilization sky rockets too. Hence, multiple births are more common in today’s society than decades ago. However, the world can only sustain so many people before it reaches it maximum. By having multiple births, it only puts other humans in greater risk of danger because it increases the rate in which our resources are being depleted. A very popular and similar case to this that still exists today is China’s one child policy. China is very populated and the environment can barely support all the humans living there. People were having too many children via natural pregnancy and other methods too which led the government to establish regulations. Overpopulation in China is the main cause for the lack of living space available and other resources such as education. There are new laws being implemented to control the number of embryos being transferred. Clinics are still allowed to transfer 2-3 embryos but if possible they will only transfer one. This makes in vitro fertilization even more costly for desperate couples who want children. On the brighter side, a decrease in multiple births will mean a decrease in birth defects for babies who compete for nutrients in multiple births.

Religion Concern: One of the major issues surrounding IVF is considered to be one of moral opinion. Ethics say in vitro not only causes problems that may potentially harm both the carrier and the babies but also suggest that multiple births may eventually lead to discarding of embryos also known as abortion. IVF is not as simple as is hoped for, problems are not rare to occur, and most likely will happen; such as the chance of multiple births. Some couples, as willing as they are to gain a child through the technology of IVF, are neither ready nor willing to take on the challenge of multiple births if the need arises. This then leads to the destruction of embryos; more famously known as abortion. Religion plays a major role in these ethics. Catholics along with many other religions agree that every child has a right to be born into a loving home with both a mother and father. New laws are now opening up restrictions about patients qualifying only if they are in a healthy heterosexual relationship, thereby causing uproar in religions worldwide. The moral in all this is the belief that children, embryos counted and all, deserve a right to live, and the right to a healthy, loving home. Although in vitro fertilization is beneficial in many ways, it also has it’s downfalls that reflect upon technology today and how potentially harmful it can be.

Interesting Facts
- Since the 1980s, more than a half-million children have been created through IVF. - About a half-million embryos are left over. - A third of the couples storing embryos have more than six. - IVF is a relatively new procedure that has been around for a little over 30 years. - Generally, in women who use IVF to establish a live birth, about 63% are single babies, 32% are twins, and 5% are triplets or more. - Babies conceived through IVF have higher rates of low birth weights and birth defects. - The average couple will need 3 attempts before obtaining a pregnancy through IVF. - In vitro is latin meaning “in glass”.

Conclusion
Although it is believed and has been proven to be effective, in vitro fertilization will almost always pose as a hazard, both on the child bearer and the baby itself. In conclusion, we believe, IVF not only is harmful but also causes controversy and issues all around. Ethically it has been proven that in vitro has a high outcome of producing multiple births which then branches off to many more problems including premature births, complications with the mother and large health care expenses. Environmentally, IVF has shown to be an issue due to the sustainability of our planet. Increasing number of births leads to a growing population which eventually results in more rapid depletion of resources and space. Lastly, backing into it from a religious point of view, in vitro fertilization becomes a massive issue of moral complication. The result of multiple births through the use of IVF is a major cause of abortion, through the unwillingness or unpreparedness of couples and or single parents to have more than one child – embryos are discarded and therefore some religions believe the whole process to be unnecessary and highly unethical. With new technology and advances within society today, the success rate of births through means of in vitro fertilization seems to be growing. But with so many complications, people do have options, such as adoption, artificial insemination, and even ovarian stimulation, each proposing its own benefits.