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ART Truth:

Must Excercise, 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.

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.

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.

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.

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.
More on egg donation

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 to not 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 treaded 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.

Intracycloplasmic 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

Very low numbers of motile sperm with normal appearance.
Problems with sperm binding to and penetrating the egg.
Antisperm antibodies (immune or protective proteins which attach and destroy sperm) of sufficient quality to prevent fertilization.
Prior or repeated fertilization failure with standard IVF culture and fertilization methods.
Frozen sperm collected prior to cancer treatment that may be limited in number and quality.
Absence of sperm secondary to blockage or abnormality of the ejaculatory ducts that allow sperm to move from the testes. In this situation, sperm are obtained from the epididymis by a procedure called microsurgical epididymal sperm aspiration (MESA) or from the testes by testicular sperm aspiration (TESA).

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.

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.

Recurrent Pregnancy Loss

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.

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.

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.