Dr L H Hiranandani Hospital : Centre for Human Reproduction

A blastocyst is an embryo at an advanced stage of physiologic development when there are two cells present: one group of cells that form the placenta, and another group of cells that form the fetus. Advances by our superb IVF laboratory staff have been able to provide proper nutrients to grow embryos to this advanced stage of development. The further the developed embryos, the better your ability to select the healthiest and most viable embryos, while transferring a smaller number of embryos. This will allow us to maintain or raise pregnancy rates while reducing the number of embryos returned by reducing the most significant complication - multiple pregnancy.

Why does the blastocyst stage have a higher implantation rate than two-to four- cell stage embryos?
Not all fetilized oocytes are normal, and therefore a percentage always exists that are not destined to establish pregnancy. The majority of such abnormalities are chromosomal. It has been determined that around 25% of the chromosomes are abnormal and that this problem worsens with maternal age. The culmination of this is that many abnormal embryos arrest or stop growing during development. So by culturing embryos to the blastocyst stage, one has already selected against all those embryos with little if any development potential. Therefore, a blastocyst has a higher implantation rate.

Exercise, Weight, and Fertility

Couples with infertility often wonder if lifestyle habits might compromise their fertility. Two important lifestyle factors, weight and exercise, can affect fertility.

Low weight or weight loss can lead to a decrease in an important hormonal "message" that the brain sends to the ovaries in women and testes in men. This hormone, gonadotropin releasing hormone (GnRH), is produced in the part of the brain called the hypothalamus. The release of GNRH leads to the release of the hormonal messengers LH and FSH (the gonadotropins) by the pituitary gland. LH and FSH are critical for the development of eggs in the ovaries and sperm in the testes. The degree to which weight loss affects fertility will vary. In mild cases, the ovaries may still -produce and release eggs, but the lining of the uterus may not be ready to receive a fertilized egg because of inadequate ovarian hormone production. In more severe cases, ovulation does not occur, and menstrual cycles are irregular or absent. In men, low weight or weight loss may lead to decreased sperm function or sperm count. If low weight or weight loss has been identified as the cause of one's infertility, the preferred treatment would be to stop losing weight or even to gain weight if needed. An alternative treatment is the use of medications. Drugs such as GnRHa(Lupride®) or gonadotropins (Pergonal®, Menogon ®, Puregon®) replace or eliminate the need for the missing message from the hypothalamus or pituitary and may restore fertility. However, the use of these drugs can be complicated, expensive, and can cause multiple pregnancies.

Being overweight or obese can affect the hormonal signals to the ovaries or testes. Increased weight can also increase insulin levels in women, which may cause the ovaries to overproduce male hormones and stop releasing eggs. Weight loss is the best plan of action, but drugs such as clomiphene citrate or gonadotropins can be used in overweight patients. It is important to make sure that glucose (blood sugar) levels in overweight patients are normal prior to attempting pregnancy and that specific metabolic causes of obesity are not present.

Proper exercise and diet are important for maintaining good health and proper weight. Extreme exercise can, however, lead to reduced sperm production in men and the cessation of ovulation in women by decreasing the brain message to the ovaries and testes. However, the amount of exercise must be very extensive; normal exercise will not affect fertility in most couples. It is impossible to know how much exercise for any one person is too much. Generally, running more than 1O miles per week is considered too much when trying to conceive. The most effective way to treat reproductive problems associated with excessive exercise is to decrease or modify the amount of exercise.

Egg Donation - Reversing the biological clock

Egg quality has remained one of the major determinants of successful IVF. Egg quality diminishes over age 35 and significantly declines over the age of 39, yielding a low chance of successful pregnancy in an otherwise healthy woman capable of carrying a pregnancy. Egg donation allows a couple to experience a significant increase in their rate of pregnancy with ability to experience a pregnancy and delivery. In egg donation IVF, the donor of eggs may be anonymous or she may be a sister, close friend, or relative or the infertile woman. The egg donor is given fertility medications to stimulate her ovaries to produce multiple eggs. Hormone replacement is used to synchronize the recipient to the egg donor's cycle. Just prior to ovulation, using standard IVF techniques, the eggs are retrieved from the donor's ovaries and fertilized with sperm of the recipient couple.

There ends the donor's brief but important role. In the IVF lab, the donor's eggs are mixed with the sperm of the father to be. Up to four embryos are transferred to the infertile woman's uterus, two or three days later. Hormone support is administered for the first couple of months to maintain the pregnancy. A pregnant recipient of donor egg IVF has a reduced rate of miscarriage or Down's syndrome.

HISTORY OF EGG DONATION
Donor egg IVF was initially developed to treat women with premature ovarian failure, women who didn't have any eggs and couldn't become pregnant. The applications of this new technology have greatly expanded. Donor egg IVF is now used for women who are carriers of genetic diseases, women who have had multiple failed cycles of IVF, women with impaired ovarian function, or for older healthy women. This treatment also heightens the chance of pregnancy for women whose attempts at IVF have revealed a poor response to fertility medications, or eggs that did not fertilize well or form viable embryos.

BENEFITS OF EGG DONATION IVF
One of the main benefits of this new reproductive technology is its high rate of success. The principle seems to be that the age of the egg, not the uterus, is the critical factor. Success rates for donor egg IVF can be three to ten times higher than with regular IVF. Much of this success is due to the use of young, normally fertile donors. Donor egg IVF offers some possible advantages over adoption. One is that couples have complete control of the pregnancy. The woman can be sure of getting excellent prenatal care and be sure to avoid alcohol, tobacco, illegal drugs, or unnecessary medications.

WHO ARE THE EGG DONORS?
Most IVF programs that use egg donors tend to use healthy, bright, responsible people. Potential donors are carefully screened for hereditary diseases, high-risk behaviors, or other medical problems. Most donors have been pregnant before, and are young and healthy. Generally, donors are compensated for all that they go through - the ultrasound exams, blood tests, and egg retrieval. Most egg donors do it because motherhood has been very positive for them and they want to share with others who haven't been able to do this on their own.

Dr L H Hiranandani Hospital - The center for human reproduction is proud to announce its comprehensive Egg Donation program utilizing the team approach. Donors are thoroughly screened both medically and psychologically in the effort to assess whether they meet the stringent guidelines established by the professional staff. There is new hope for women who have premature ovarian failure, age, or genetic considerations. The success rate using donor eggs is far greater for these women than In Vitro Fertilization, where they use their own eggs. Although the odds are significantly better, they unfortunately are not 100%.

Recipients are interviewed and counseled regarding the medical and psychosocial implications of the process. Introductions and matches are made by consent of both parties. Egg donation is said to be a new reproductive cure which enables patients to achieve their dream, to bear and nuture a child. Egg donation provides a means for the medical community to turn back the biological clock of women nearing the end of their reproductive years.

The old tradition of donation is based on anonymity, secrecy, and non-disclosure. However, there is one question that emerges as the foremost in recipients minds when they begin to contemplate egg donation. The issue of anonymous verses non-anonymous donation. Tradition and experience have led us to develop a program that offers only anonymous donors.

Whether one turns to egg donation or not, depends on the medical diagnosis. In consultation with your physician, the decision should be made whether you are psychologically prepared to be a candidate. This means being ready to make a commitment to parenting a child that is genetically related to only one of you. It also involves asking yourself and your partner some hard questions, which deserve some very honest answers. These questions will be extremely difficult ones. Who to tell or not to tell; when to tell; the non-genetic relationship disclosure issues, and what to tell the child, are all important questions that need to be discussed.

If you have any questions concerning the Egg Donation Program, please feel free to call our office for more information. We look forward to working with those patients who find egg donation to be their option and making their experience a rewarding one.

Medical Protocol
Perhaps a preface to this guide should be a reminder that fertility and achieving a pregnancy is not an exact science. There are so many unknown factors influencing fertility, that even with all the advances in reproductive technology conception remains as much an art as a science Each doctor has his own protocol, and the couple or donor's reaction to the drugs may result in a change in protocol. Following is a sample schedule for an egg donor and an egg recipient couple.

The start of a menstrual cycle is referred to as DAY ONE (1) of the cycle. In an average 28-day cycle, a woman will most likely ovulate around day 14. This means the egg retrieval will usually take place on day 14 and the transfer will take place on day 16 or 17. According to the treating physicians instruction, the egg donor will undergo ovulation induction. It is a procedure that involves the administration of fertility drugs to produce multiple egg (follicle) development. Fertility drugs are administered by injection or sometimes taken orally. There are two drug protocols that physicians use.

[FLARE UP] This protocol begins on the third day of the donor's menstrual cycle, and continues for seven -to ten days. During this time hormone levels will be monitored by means of blood tests and follicle development will be followed by means of transvaginal ultrasounds.

[DOWN REGULATION] This protocol begins around the 20th day of the previous cycle. The physician will temporary "turn off" the ovaries using Lupride to promote better egg development.

When the follicles containing the eggs reach the requisite size, an injection of HCG is administered to prepare them for aspiration. The egg retrieval/aspiration is performed in a hospital like facility under sedation. A vaginal ultrasound probe is utilized for aspiration of all ovarian follicles. This is a non-surgical procedure that takes about twenty to thirty minutes, depending on how many eggs are retrieved. However, the donor should plan to spend at least three hours at the clinic. After a brief period in the recovery room, the donor will go home that same day.

It is important that you do not blame yourselves or each other, if a pregnancy is not achieved in any given cycle, Fertility is not an "all or nothing" proposition - it's a matter of degree. Unfortunately, there are factors that are unknown and therefore, no one has any control over that which can affect conception.

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Side Effects of Gonadotropins

There are many types of gonadotropins used alone or in combination for ovulation induction. They include hMG (human menopausal gonadotropin Humegon®), FSH (follicle stimulating hormone Gonal-F®) and hCG (human chorionic gonadotropin, Profasi® )with the use of these drugs, careful monitoring is required to minimize the side effects, discussed below.

1. Ovarian Hyperstimulation (OHSS)
Occurring in 1 to 5 percent of patients the chance of OHSS is increased in women with polycystic ovarian syndrome and in conception cycles. When severe, it can result in blood clots, kidney damage, ovarian twisting (torsion), and chest and abdominal fluid collections. In severe cases, hospitalization is required for monitoring, but the condition is transient, lasting only a week or so. Occasionally, drawing fluid out of the chest or abdominal final cavity helps. The best prevention is not to give hCG to induce ovulation at the end of an overly vigorous stimulation cycle.

2. Multiple Gestations
Up to 20 percent of pregnancies resulting from gonadotropins are multiple, in contrast to a rate of 1 to 2 percent in the general population. Although most of these pregnancies are twins, a significant percentage are triplets or higher. High-order multiple gestation pregnancy is associated with increased risk of pregnancy loss, premature delivery, infant abnormalities, handicap due to the consequences of very premature delivery, pregnancy induced hypertension, hemorrhage, and other significant maternal complications.

3. Ectopic (Tubal) Pregnancies
While ectopic pregnancies occur 1 to 2 percent of the time, in gonadotropin cycles the rate is slightly increased at 1 to 3 percent. These can be treated with medicine or surgery. Combined tubal and intrauterine pregnancies (heterotopic pregnancies) occasionally occur with gonadotropins and need to be treated with surgery.

4. Birth Defects
The rate of birth defects after gonadotropin cycles is not higher than in the general population, at 2 to 3 percent. Furthermore, these children are developmentally no different than their peers.

5. Adnexal Torsion (Ovarian Twisting)
Less than 1 percent of the time, the stimulated ovary can twist on itself cutting off its own blood supply. Surgery is required to untwist or even remove the ovary.

6. Gonadotropins and Ovarian Cancer
The risk of ovarian cancer seems in part related to the number of times a woman ovulates. Infertility increases this risk; birth control pill use decreases it. Controversial data exists that associates ovulation stimulation drugs like gonadotropins with the risk of future ovarian cancer. While research is underway to help clarify this issue, the careful use of gonadotropins is still reasonable, especially considering that pregnancy and breast feeding reduce cancer risk.

Pregnancy Rates in Assisted Reproduction

You will need to be familiar with the following terms in order to understand pregnancy rates. Cycles initiated - The number of couples which began to take fertility medication for the purpose of doing IVF. Retrievals - The number of couples who successfully completed the medication phase and had an egg retrieval performed NOT ALL COUPLES WHO START THE MEDICATION PHASE WILL MAKE IT TO EGG RETRIEVAL.

Transfers - The number of couples who successfully completed the medication phase, underwent egg retrieval, and had normal Fertilization and growth with the resulting transfer of at least one embryo to the uterus. NOT ALL COUPLES WHO UNDERGO AN EGG RETRIEVAL WILL HAVE EMBRYOS TO TRANSFER TO THE UTERUS. Male factor - Any abnormality in the semen that could result in lower fertilization rates. This includes low sperm counts, low sperm motility, or a high degree of morphologically abnormal sperm.

Egg factor - Any problem which a woman may have that lowers the quality of her eggs and therefore reduces the chance for a successful pregnancy. This category includes women of advanced age, elevated FSH (Follicle Stimulating Hormone), poor stimulation with fertility medications, and/or poor quality of the eggs when viewed under a microscope.

"Mature" Oocytes - Not all eggs that are retrieved during an ART cycle are capable of being fertilized, Viewing under a microscope determines those eggs which will be selected to attempt fertilization. The percentage of mature Oocytes can vary from patient to patient and cycle to cycle. Fertilization Rate - The number of embryos which demonstrate NORMAL fertilization (two pronuclei seen) divided by the number of MATURE Oocytes which had sperm added or injected.

Clinical pregnancy rate - A pregnancy which has developed far enough along so that it can be visualized as a gestational sac on ultrasound. THIS DOES NOT INCLUDE PREGNANCIES OUTSIDE THE UTERUS (ECTOPIC) OR PREGNANCIES THAT DON'T REACH THE STAGE WHERE THEY CAN BE SEEN ON ULTRASOUND (SO-CALLED BIOCHEMICAL PREGNANCIES). We use clinical pregnancy rates as a standard for comparisons only. NOT EVERY COUPLE THAT HAS A CLINICAL PREGNANCY WILL DELIVER A BABY, SOME WILL STILL HAVE A MISCARRIAGE.

Assisted Hatching in IVF

Assisted hatching is an IVF technique in which the zona is treated prior to embryo transfer in order to weaken the wall of the embryo and thus improve the likelihood of successful hatching and embryo implantation. The zona pellucida (egg shell) has a complex structure that envelopes the egg/embryo. In nature, about two days after an embryo reaches the uterus, the zona opens and all the embryonic cells hatch out, which then try to burrow into the endometrium to establish the implantation. This is known as hatching.

The inefficiency of human in vitro fertilization (IVF) is largely due to implantation failure. Possible causes of this failure of embryos to implant successfully include :

Indications for assisted Hatching

Assisted hatching is generally performed on the third day of embryo culture. Briefly, the microscopic assisted hatching procedures was accomplished by blowing the chemical zona-drilling solution (an acidified buffer) very slowly and gently over the surface of the zona to create an opening in the zona. The zona-drilled embryos are then rinsed several times in fresh culture medium before returning them to standard culture conditions inside the IVF laboratory prior to the embryo transfer. We now perform laser assisted hatching wherever indicated.
With this latest technology and the expertise of our IVF staff, we have had great success with achieving pregnancies for many couples who may never have an opportunity for successful parenthood

Prediction of Fertility Potential in Female Patients

A woman's reproductive potential declines with age. This is reflected in the decreased ability to conceive (become pregnant) with increase in the rate of spontaneous abortions (miscarriages). Although fecundity (the ability to achieve a pregnancy that results in a live birth) decreases in all women as they age, the precise age when a woman can no longer conceive varies between individuals. Approximately one-third of couples in which the female partner is age 35 or older will have problems with fertility. It is estimated that two-thirds of women will not be able to get pregnant spontaneously by the age of 40. Several tests may be useful in assessing fertility potential in older patients. For those patients with poor fertility potential predictions, the use of donor eggs or embryos can be considered.

Day 2/3 levels of FSH, LH, and estradiol
The determination of blood concentrations of follicle stimulating hormone (FSH), and estradiol levels on menstrual cycle day 2/3 has been used to estimate fertility potential. Women with elevated levels of FSH and/or estradiol measurements on cycle day 3 have very poor pregnancy rates with both ovulation induction and assisted reproductive technologies (ART such as in vitro fertilization (IVF). More recently, it has been shown that women with elevated blood levels of luteinizing hormone (LH) on cycle day 3 also have poor pregnancy outcomes with fertility therapy.

Clomiphene citrate challenge test
This test entails the oral (by mouth) administration of 100 milligrams of clomiphene citrate on menstrual cycle days 5-9. Blood levels of FSH are measured on cycle day 3 and again on cycle day 1O. Elevated blood levels of FSH on cycle day 3 or cycle day 1O are associated with very low pregnancy rates with both ovulation induction therapy and ART.

Response to Gonadotropins
Gonadotropins (Pergonal®, Humegon® and Nenogon®) are concentrated mixtures of FSH and LH or FSH alone (Puregon®, Recagon® or Gonal-F®) which are given as injections to stimulate the ovary to produce multiple eggs in preparation for various fertility therapies. The amount of gonadotropins required to induce egg development increases with increasing chronological age. Patients requiring large amounts of gonadotropins to induce egg development generally have lower pregnancy rates with both ovulation induction therapy and ART.

Several laboratory methods are currently used to measure blood levels of FSH, LH and estradiol. Measurement of these hormone levels may vary considerably depending upon the particular laboratory method used. Therefore, it may be difficult to compare blood levels of these hormones that are measured at different laboratories or by different laboratory techniques. It is important that normal and abnormal test values be based on the pregnancy rates achieved by women studied at a particular center using the same laboratory methods.

Stress and Infertility

Stress is defined as any event that a person perceives as threatening or harmful. Stress can result in the heightened activity of many body organs. This increased activity is offset by hormones by the adrenal glands and through the nervous system. Acute stress can result in increased heart rate, blood pressure and respiration, as well as sweaty palms and cool, clammy skin. Chronic stress can also cause depression and result in changes in the immune system and sleep patterns.

STRESS CAUSING INFERTILITY
Although infertility is a highly stressful experience, there is very little evidence that infertility can be caused by stress. In rare cases, high levels of stress in women can change hormone levels and cause irregular ovulation. Some studies have shown that high stress levels may also cause fallopian tube spasm in woman and decreased sperm production in men.

INFERTILITY CAUSING STRESS
Research has shown that women undergoing treatment for infertility have a similar, and often higher, level of "stress" as women dealing with life-threatening illnesses such as cancer and heart disease. Infertile couples experience chronic stress each month, first hoping that they will conceive and then dealing with the disappointment if they do not.

WHY INFERTILITY IS STRESSFUL
When diagnosed with infertility, many couples no longer feel in control of their bodies or their life plan. Infertility can be a major crisis because the important life goal of parenthood is threatened. Most couples are accustomed to planning their lives. Experience has shown that if they work hard at something, they can achieve it. With infertility, this may not be the case. Infertility testing and treatments can be physically, emotionally and financially stressful. A couple's intimacy is often reduced by the infertility experience, which further contributes to increased stress levels. Trying to coordinate medical appointments with career responsibilities can also increase pressures on infertile couples.

TIPS FOR STRESS REDUCTION

Intracytoplasmic Sperm Injection (ICSI)

Intracytoplasmic sperm injection (ICSI) is a laboratory procedure developed to help infertile couples undergoing in vitro fertilization (IVF) due to severe male factor infertility. ICSI involves, the insertion of a single sperm directly into the cytoplasm of a mature egg (oocyte) using a microinjection pipette (glass needle). ICSI has largely replaced the two previously developed micromanipulation techniques because it achieves higher overall fertilization rates.

A variety of sperm problems can account for male infertility. Sperm can be completely absent in the ejaculate (azoospemia) or present in low concentrations (oligozoospermia). They may have poor motility (asthenospermia) or an increased percentage of abnormal shapes and forms (teratospermia). There may also be abnormalities in the series of steps required for fertilization, such as sperm binding to and penetrating the egg. Deficiencies in any of these aspects of sperm function will generally lead to lack of fertilization.

ICSI can facilitate fertilization by sperm that will not bind to or penetrate an egg. It can also be used to treat men with extremely low numbers of sperm. However, ICSI is generally unsuccessful when used to treat fertilization failures that are primarily due to poor egg quality.

INDICATIONS FOR INTRACYTOPLASMIC SPERM INJECTION

ICSI is not a perfect technique. Some eggs will be damaged by the ICSI process. Some eggs have plasma membranes that are difficult to pierce. In other instances, the fertilized egg may fail to divide, or the embryo may arrest at an early stage of development. Egg fertilization rates of 50 percent and cleavage rates of 80 percent or more are expected, but only 15 to 20 percent of egg retrievals produce a baby in well-selected couples.

Perinatal outcome studies in Europe suggest that although multiple pregnancies are common in ICSI, there is to date no evidence of increased incidence of congenital malformations or abnormal karyotypes. There is no evidence that abnormalities may arise later in life to babies born as a result of ICSI, although there is also no guarantee that all babies will be normal. For example, because some causes of male infertility are unexplained and/or related to genetic problems, male offspring might have reproductive problems as an adult. Furthermore, approximately 1 in 20 individuals in the general population will have some birth defect and this risk is likely to be similar in babies born as a result of the ICSI procedure.

Counseling and Support

Infertility is a medical condition that touches all aspects of a person's life. It affects how you feel about yourself, your relationship with others, and your perspective on life. How you deal with these feelings will depend on your personality and life experiences. Most people can benefit from the support of family, friends, medical caregivers, and professional counselors. The following information will help you decide if you need to seek professional help in managing the emotional stresses associated with infertility.

WHEN DO I NEED TO SEE AN INFERTILITY COUNSELOR?
Consider counseling if you are feeling depressed, anxious, or so preoccupied with your infertility that you feel it is hard to enjoy life. You may also want to consider counseling if you are feeling "stuck" and need to sort out your options and alternatives. Signs that you might benefit from counseling appear in combination and may include :

WHERE CAN I GET SUPPORT?
Support can come from many different areas. Books can offer information and understanding about the emotional aspects of infertility. Support groups and meetings can reduce the feeling of isolation and provide an opportunity to learn from others who are experiencing infertility. Individual and couple counseling offers the chance to talk with an experienced professional who will help sort out your feelings, identify coping mechanisms, and help you find solutions to your problems.

Multiple Gestation and Pregnancy Reduction

Multiple gestation refers to a pregnancy in which two or more fetuses are present in the womb. In the general population, this occurs in approximately 1 to 2 percent of pregnancies. However, with the use of fertility drugs such as clomiphene citrate or gonadotropins and high-tech, procedures such as in vitro fertilization (IVF), multiple gestations are much more common. The vast majority of these pregnancies are twins, but triplets, quadruplets, and higher numbers can occur.

Fetal risks of multiple gestation include an increased chance of miscarriage, birth defects, premature birth and the mental and/or physical problems that can result from a premature delivery. The average length of pregnancy is 39 weeks for a single gestation; 35 weeks for twins; 33 weeks for triplets; and 29 weeks for quadruplets. In general, the risks of complications due to premature delivery are significantly less once the pregnancy reaches 32-34 weeks gestation. Maternal risks due to multiple gestation include premature labor, premature delivery, pregnancy-induced high blood pressure or pre-eclampsia (toxemia), diabetes and vaginal/uterine hemorrhage.

Multifetal pregnancy reduction is a technique that reduces the number of fetuses in an effort to increase the likelihood that the pregnancy will continue. Consequently, the risks to the mother and remaining fetuses are reduced. This procedure is more likely to be performed when there are four or more fetuses present. The number of fetuses is often reduced to two, although in some circumstances they may be reduced to one. Because triplets and twins generally do better than higher-order multiples, reduction in these cases is rarely recommended, although it may be considered under special circumstances.

Multifetal pregnancy reduction is usually performed between 9 and 12 weeks gestation. The procedure is most successful when performed early in the pregnancy. It is done on an outpatient basis by inserting a needle guided by ultrasound through the abdomen or vagina to inject potassium chloride into the fetus. The incidence of miscarriage associated with this procedure is 4 to 5 percent. Premature labor occurs in about 75 percent of multifetal pregnancy reduction pregnancies. Miscarriage of the remaining fetuses and maternal infection rarely occur.

Dealing with the decision of whether or not to undergo multifetal pregnancy reduction can be a traumatic experience. Couples who have invested a great deal of time, money and energy in pursuing pregnancy are often unprepared to make this decision. It is usually helpful for couples considering multifetal reduction to undergo professional counseling prior to undergoing the procedure. Both partners need to be comfortable with their decision and may need emotional support prior to and immediately following the procedure.

Recurrent Pregnancy Loss

Introduction
Pregnancy loss, more commonly referred to as "miscarriage", is the most common complication of pregnancy. Approximately 10-15% of all first-time pregnancies result in miscarriage. In most instances, you can expect a similar miscarriage rate in subsequent pregnancies. Recurrent pregnancy loss is commonly defined as 3 or more miscarriages. Approximately 5% of couples attempting pregnancy have recurrent pregnancy loss. In the past, few couples were diagnosed with a specific cause for miscarriage. Recently, progress has been made in understanding recurrent pregnancy loss that was previously unexplained.

Diagnosis
The most important part of treating couples with recurrent pregnancy loss is determining the cause or diagnosis. Causes of recurrent miscarriage include chromosomal defects, uterine defects, hormone deficiencies, and immunological factors. At Rotunda, we conduct a thorough evaluation of each couple to determine the cause of miscarriage. After diagnosis has determined a cause, the correct treatment plan can be discussed and decided upon.

Chromosomal Abnormalities
Chromosomal abnormalities can be caused by abnormalities that exist in the genetic structure of one or both parents. These abnormalities are not life threatening to the parents, but when passed to the embryo, they can cause miscarriage. Chromosomal analysis of both partners can be done to determine if abnormalities exist by actually looking at the chromosomes of blood cells from both partners. Other abnormalities can result during conception and will only exist in the growing embryo. If miscarriage occurs, the cells from the embryo can be tested to determine the existence of abnormalities.

Most usually, chromosomal abnormalities are not treatable. Genetic counseling can offer guidance to couples on the chances of passing abnormalities to their children. Couples can then make informed decisions about continuing to try to conceive using their own eggs and sperm, trying donor eggs or sperm, looking further into adoption, or remaining childless.

Uterine Defects
Defects of the uterus can be caused by several factors. Some women are born with defects in the structure of the uterus caused by genetics or exposure in utero to certain chemicals. The most well known defect caused by a chemical is that of DES. DES is an estrogen like compound used from the 40's through the 70's to treat complications of pregnancy. Children born with this treatment experienced fetal anomalies, including defects in the uterus.

Other defects can be caused by polyps (small growths in the uterine lining) or fibroids, which can cause problems with implantation of the embryo or retard the growth of the fetus, eventually leading to miscarriage. Uterine defects can be diagnosed using hysterosalpingography, a procedure in which dye is injected into the uterus and then photographed using an X-ray (see Testing and Diagnosis). Treatment may include surgery to go in and reshape the uterus or remove polyps or fibroids.

Hormone Deficiencies
This is an uncommon deficiency associated with very early abortion. The cause is an inadequate corpus luteum (yellow body) functioning on the ovary at the place of ovulation (the old follicle), which is the gland that produces progesterone during early pregnancy. Progesterone is the hormone that is necessary to maintain the pregnancy. If this hormone is not present in sufficient quantities, the pregnancy will abort, sometimes even before it is detected.

Women experiencing a luteal phase defect often have this problem. Luteal phase defects are also caused by a lack of progesterone produced by the corpus luteum during the cycle. Luteal phase defects can be detected by endometrial biopsies and serum progesterone levels during the luteal phase.
This type of hormone deficiency can be treated with supplemental progesterone given during the luteal phase or the first trimester of pregnancy when an inadequate corpus luteum is suspected. Supplemental progesterone is also given during superovulation cycles such as IVF or GIFT to counteract the increased levels of estrogen produced by multiple follicles. Progesterone supplementation is often maintained through the first trimester of these pregnancies to ensure adequate levels.

We have also seen situations where endometrial thickness is poor, although the composition is normal. Optimal endometrial thickness is 8-13mm at the time of the LH surge. We have come to suspect that certain patients may be deficient in estrogen or response to estrogen. This estrogen is required to build up the lining in the first half of the cycle. Thin endometrial linings have been associated with recurrent miscarriage and estrogen inadequacy may be the cause. This may be treated with superovulation with or without supplementation with Viagra.

Immunologic Factors
This is one of the newest and sometimes most controversial problems associated with recurrent pregnancy loss. Autoimmune problems where the body produces antibodies against other body proteins has been linked to miscarriage. These problems are diagnosed by tests such as Anti-Nuclear Antibodies (ANA) and Anti-Phospholipid Antibodies (APA), which detect the presence of these antibodies in the woman's blood. These antibodies may cause an abnormal clotting event to occur during pregnancy, which causes interruption of the blood flow to the placenta. As this interruption becomes more and more severe, the fetus begins to starve for oxygen and nutrients and eventually dies. This eventually leads to miscarriage.
Other problems with blood coagulation have recently come to light as being associated with both infertility and recurrent miscarriage. These all have the same basic outcome by clotting off the placenta and causing miscarriage at various stages in the pregnancy.

The most notable treatment for immunologic factors of miscarriage is the administration of low dose aspirin, heparin, and steroids. These reagents cause a masking effect that can help prevent clotting off the placenta. While the benefits from this treatment remain controversial in the medical community, our experience with patients has led us to believe that many patients receive a benefit from this treatment. This benefit has been realized in a dramatic increase in the number of pregnancies achieved and delivered after we initiated a more general use of this treatment.

In a large group of patients, who were previously diagnosed as unexplained infertile or unexplained miscarriage, our work with hematologists has shown an association between pregnancy loss, infertility, and certain coagulation disorders. Empirical treatment for the diagnosis of these coagulation disorders by the use of aspirin and heparin has been offered to our patients. While patient caution is indicated, we feel there are great benefits associated with this treatment.

Centres of Excellence

Art Truths ( Artificial Reproduction Techniques )

IVF Blastocyst Transfer