Advances in Male Fertility

By: Ash Kshirsagar, MD

Infertility is a challenge that burdens roughly 1 in 5 couples. It can be a very sensitive and emotionally frustrating issue causing stress in an otherwise healthy relationship. Guilt, resentment, and inadequacy can surface impairing the intimacy between a couple and hinder the support a couple needs from one another in facing such an issue. Historically, the focus and burden of infertility treatments has focused on the female partner.

Of all infertile couples, the reason for the infertility will lie within the male in about 10-15% of the cases. Because of this, a new field of medicine has emerged that is known as Male Infertility. A male infertility specialist is a urologist who has received additional formal training (a fellowship) to learn how to treat men with fertility problems. Fortunately, recent advances in this field can offer men hope of fathering their own biological children.

The major advances in the field focus on accurate diagnosis and use of the newest technology to improve success of finding sperm. The accurate assessment of men with infertility problems includes ensuring the male doesn't have a hormone imbalance or underlying medical condition impairing sperm production. Additionally, a detailed review of prescription medications must be done to check for unwanted interaction with medications and sperm production.Using the latest genetic testing, one can predict which men are candidates for surgical sperm retrieval and which men are not. In the assessment of the male, we can also determine with greater than 90% accuracy which men have a blockage in their tubes. The main advantage that a male fertility specialist can offer is using the most cutting-edge technology: this resides in using a true operating microscope to improve outcomes for patients while decreasing complications. An operating microscope is a free standing real microscope that is used during surgery to treat conditions such as a varicocele (the most common cause of infertility in men) or to find sperm in men who were otherwise thought to have none. The operating microscope provides 15 times the magnification compared to that of the human eye. Studies have shown that when an operating microscope is used, complications such as bleeding decrease and success rates in finding sperm increase substantially. This translates to finding sperm in men who were otherwise resigned to the thought they would never have their own biological children.

Using the operating microscope, the male infertility specialist can also improve the success rates of vasectomy reversal surgeries to over 90%. The vasectomy reversal is one of the most technically challenging surgeries a urologist performs. A male fertility specialist has received dedicated formal training in microscopic surgery for this specific surgery. During the surgery, the two ends of the vas are sewn back to each other using sutures finer than a human hair. Given the delicate nature of the surgery, studies have shown that a surgeon who implements the latest technology of the operating microscope can provide the best success rates for patients.

What is Turner Syndrome?

By: Sunita Kulshrestha, MD, FACOG

Turner syndrome is a genetic condition that affects females. Rather than having inherited two normal X chromosomes, one copy of the X chromosome is missing or significantly altered. Turner syndrome is one of the most common chromosomal abnormalities in pregnancies but the majority of conceptions end in a miscarriage. The incidence of Turner syndrome in live births is 1 in 2,000-5,000.

Signs and symptoms of Turner syndrome may vary significantly. In some young girls, a number of physical features and poor growth are apparent early in life. For others, the presence of Turner syndrome may not become apparent until the onset of puberty with abnormal pubertal or sexual development. The majority of women with Turner syndrome have ovarian failure and thus infertility or premature menopause. In addition to these abnormalities, patients with Turner syndrome can also have hearing loss and abnormalities involving the heart, kidney, endocrine system, gastrointestinal system, and skeletal system.

Occasionally, patients with Turner syndrome achieve pregnancy spontaneously or with assistance, but these pregnancies are high risk pregnancies for the mother and need to be followed closely.

Disclosure in Anonymous Donor Egg IVF

By: Laurence C. Udoff, MD, FACOG

I am often asked what part of my job I find the most gratifying. Though in general, I consider it a privilege to play a role in the care of all of my patients, working with donor egg IVF patients offers special rewards for both the patient and the caregiver. In most situations, the use of donor egg IVF has the most dramatic impact on a patient's chance for conception. In many cases a patient may be told there is little to no chance for success without donor egg IVF. With donor egg IVF, clinical pregnancy rates per attempt are 60-70%. It is usually the most successful form of treatment we can offer. Though a miracle for many, it is clearly not the right choice for everyone. There are many issues to consider, as obviously the donor egg recipient and "birth mother" is not the "genetic mother." There are also the issues of disclosure with anonymous egg donation. Do you tell friends, family and the child the identity of the "genetic mother?"

To address this often difficult question, a review article was recently published that closely examined the issue of disclosure in assisted reproduction involving donor sperm or donor egg IVF. This article summarized recent studies that assessed the impact of disclosure on egg or sperm donors, intended parents and offspring. The following represents excerpts of the study findings related to intended parents and offspring in donor egg IVF cycles. The impact of disclosure on egg and sperm donors has not yet become a major issue in the United States. However, in countries such as the United Kingdom where a donor registry is in place and a voluntary exchange and contact registry is proposed, the number of available donors is declining.

Two recent studies have been published examining how donor egg recipients make decisions about disclosure. In the first study, 79 couples undergoing donor egg IVF underwent an in-depth interview regarding how they dealt with disclosure issues. In approximately half of the couples interviewed, there was a difference in opinion regarding whether or not to tell friends, family or the child that the pregnancy was a result of donor egg IVF. Interestingly, by the end of the study, 95% of couples were able to reach a united decision about disclosure. This suggests that it is fairly common for a couple to initially disagree about disclosure in the setting of donor egg IVF. However, using a host of resources including professional counseling, the vast majority of couples reach an agreement. In the second study, in-depth interviews were conducted with women who conceived through the use of donor egg IVF. From these interviews, two main themes were noted. One was described as "engaging in selective disclosure"- patients would decide what information to disclose and to whom. The other theme was described as "responsibility toward the resulting child." For women that disclosed, this meant the right of the child to know. Non-disclosing and undecided women voiced concerns about the negative impact on parental relationships and possible social stigma and did not see a benefit from disclosing to offspring.

Regarding what is best for the child conceived through donor egg IVF, very few studies have adequately addressed this issue. Golombok and colleagues evaluated 48 families with a child conceived through donor egg IVF (also included were children born through donor sperm and naturally conceived children for comparison). They noted that 54% of families with children conceived through donor sperm or donor egg IVF intended to disclose, 46% did not plan to disclose or were undecided. No differences in parent-child relationships were noted between those families that did not disclose and those that did. However, study conclusions were limited as the children were only 2 years old. Subsequent reports from this group have evaluated families and their children at age 4-5 and 12 years old. At an approximate age of 4-½ years old, children conceived through donor egg IVF were not experiencing increased levels of psychological problems. At age 12, a time at which psychological problems might be expected to develop based on the experience of adopted children, donor egg children continued to show no evidence of psychological problems as assessed by direct interview and questionnaires. Interestingly, at the time of the study, only 6 out of the 17 families studied had already told, or planned to tell their child that they were conceived through donor egg.

Though the issue of disclosure can be a difficult one, patients should be comforted in knowing that research to date has not been able to document any adverse affects on the family or the child, regardless of how a patient approaches the issues of disclosure. However, it must be noted that this research is still in the preliminary stages and that hopefully, future studies will provide more definitive data.

Endocrine Disruptors and Reproductive Function - Is Your Water Bottle Making You Infertile?

By: Ervin E. Jones, PhD, MD, FACOG

The term "Endocrine Disruptor" is use to describe a class of chemicals that act as agonists or antagonists of estrogens, androgens and thyroid hormones. The term has evolved to encompass hundreds of chemicals. Endocrine disruptors are foreign substances that perturb normal endocrine processes by mimicking the activity of natural hormones and, thereby, disrupt the synthesis, metabolism and functions of natural hormones.

Xenoestrogens as Endocrine Disruptors

The prefix "xeno" is derived from the Greek word "xenos" which means stranger or foreign. Thus, xenoestrogens are, by definition, estrogens that are foreign to the body. Included among the xenoestrogens discussed here are phthalates, bisphenols, organotins, phytoestrogens and diethylstilbesterol. Phthalates are compounds used in a wide variety of consumer products including plastics, adhesives, deforming agents, solvents, lubricants, vinyl upholstery, table cloths, shower curtains, rain coats, personal care products and children's toys. Phthalates are also used in some approved medical devices such as tubing, blood packs and dialysis equipment as well as surgical gloves. Globally, more than 18 billion pounds of phthalates are used each year. Phthalates can readily leach out of plastics since they are not chemically bound to the plastic matrix. Because of their widespread use in consumer products, phthalates are widely distributed in the environment and their potential for incorporation by oral, dermal, inhalation and intravenous means is high.

Bisphenols are organic compounds made by condensing acetone with phenol. Bisphenols are also widely used in plastics and plastic additives. One cross sectional study found bisphenols in 92.6 percent of the United States population examined. Organotins are compounds that contain tin linked to hydrocarbons. Organotins represent another class of widespread persistent organic pollutants with potent endocrine disrupting properties. Organotins are also used in polyvinyl chloride products as stabilizers and, therefore, may come in contact with packaged food products. Organotins bind to receptors that play key roles in fat homeostasis and adipogenesis and are, therefore, potent endocrine disruptors.

Although synthetic chemicals have received the most attention as endocrine disruptors in recent years, substances produced in nature may also function as endocrine disruptors. A notable example is the group of plant hormones known as phytoestrogens. Certain plant hormones are xenoestrogens and are found in many foods such as soy and food supplements. Diethylstilbesterol (DES) was the first recognized and only clearly documented xenoestrogens clearly linked to human disease. The synthetic estrogen was administered to pregnant women in the 1950s and 1960s to prevent miscarriage. DES was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market in 1971. Girls exposed to DES showed a high incidence of vaginal abnormalities, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. Boys exposed to DES showed Testicular Disgenesis Syndrome which is characterized by hypospadias (posterior displacement of the urethral opening on the penile shaft), undescended testes and low semen quality.

Endocrine Disruptors and Male Reproduction

According to some epidemiological studies the quantity and quality of human sperm has decreased during the last 60 years. In humans, although the causes are not clear, hypospadias has doubled from 1970. Sperm counts decreased and testicular cancer incidence increased. Global declines in semen quality were suggested to be associated with enhanced exposure to environmental chemicals that act as endocrine disruptors as a result of our increased use of pesticides, plastics, and other materials. Adult men exposed to certain phthalate esters were found to have lower levels of testosterone when compared to unexposed controls. Studies using animal tissues support these observations. In utero exposure of rats to the phthalates resulted in dose -dependent decreases in testosterone production in testis tissue obtained from adult rats.

Endocrine Disruptors and Female Reproduction

Recent epidemiologic evidence suggests that women have a unique exposure profile to phthalates. These high levels may be due to the fact that certain phthalate derivatives are used in many beauty products including perfumes, lotions, and nail polish. A study reported by the Centers for Disease Control found that reproductive age women had significantly higher concentrations of phthalate esters in their urine when compared with age- and sex-matched controls. Exposure to high levels of phthalates is associated with decreased pregnancy rates and higher miscarriage rates in female factory workers. Ovarian intrafollicular processes may be targets for environmental endocrine disruptors. Recent studies using animal models have shown that certain phthalates disrupt follicle stimulating hormone induced cumulus cell expansion, oocyte maturation in vitro and alters progesterone production in animal models. An increase in aneuploidy was found coincident with abnormal alignment of chromosomes on the meiotic spindle.

Cells obtained from human ovarian follicles during IVF procedures are steroidogenically active and respond to FSH and LH stimulation. Phthalates disrupted estradiol and progesterone production in these cells, suggesting that certain phthalate derivatives act as specific inhibitors of estradiol production in human granulosa cells. As the in vitro effective doses of the compound were within the range of real environmental exposure levels an inhibitory effect of estrogen production in vivo seems possible.

Obesity has become a global health crisis. Several studies have highlighted the link between obesity and infertility. Obesity contributes to anovulation and menstrual irregularities, reduced conception rates, reduced response to fertility treatment and to increased rates of miscarriage. A set of candidate endocrine disruptors referred to as obesogens (diethylstilbestrol, bisphenol A, phthalates and organotins among others have been proposed. These putative obesogens bind to receptors that play key roles in fat homeostasis and the genesis of adipose tissue. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology and endocrine systems to derail the mechanisms essential to weight control. Implantation pregnancy and live birth rates were poor in obese women. Pregnancy and live birth rates were reduced progressively as weight increased. Pregnancy rates in overweight women were approximately half those of normal women.

Conclusions

Endocrine disruptors are natural or synthetic compounds that perturb certain normal endocrine functions Taken together, the key deficits that appear to be imposed on fertility by environmental endocrine disruptors include abnormalities of hormone production, egg maturation and maintenance of pregnancy. Although somewhat controversial and inconclusive, the findings indicating adverse effects of endocrine disruptors on reproduction are compelling. Infertile couples and their health care providers must take in to account the potential impact of life style issues, dietary habits, and potential environmental exposures on reproductive performance.

What is ICSI?

By: David S. Karabinus, PhD, HCLD

ICSI, pronounced "Ick-See", is an acronym for Intra-Cytoplasmic Sperm Injection, a microscopic procedure where a single sperm is injected into an egg. Normally for a sperm to fertilize an egg, a sperm has to swim to the egg, penetrate the cells surrounding the egg, penetrate the covering of the egg, and penetrating egg cell membrane. ICSI does all this work for the sperm to make sure the sperm DNA is delivered to the egg. ICSI is performed in circumstances when the number of sperm is insufficient for fertilization to reliably occur, when the sperm's ability to fertilize the egg is impaired, or when the egg is known to resist sperm penetration. ICSI does not require the use of ejaculated sperm; sperm surgically retrieved from the testes or epididymides may be used. Before the development of ICSI, donor sperm, adoption, or childlessness were the only options for men who produced low numbers of sperm or functionally impaired sperm.

Personal Egg Banking (Elective Oocyte Cryopreservation)

Not quite ready to start a family?
Give yourself time, save your eggs with Personal Egg Banking

When a woman wishes to start a family is a personal choice, but it’s no secret that fertility typically declines with age. Decreased ovarian reserve is a result of the natural aging process as the number of eggs with the potential to produce a successful pregnancy declines.

That’s why the Genetics & IVF Institute is pleased to offer Personal Egg Banking (also known as Elective Oocyte Cryopreservation) as a proactive means for women to preserve their future fertility. This is accomplished by giving women the option of cryopreserving, or freezing, their eggs until they are ready to use them. So, a woman could potentially freeze her eggs at age 32 and choose to use them several years later to achieve pregnancy.

While there are no guarantees that a frozen egg will lead to a pregnancy and live birth after thaw, Personal Egg Banking can increase a woman’s chances of conception later in life with her own eggs. Current management of age-related infertility includes the use of In-Vitro Fertilization (IVF) with a woman’s own eggs, or Donor Egg IVF where eggs are obtained from a younger, more fertile donor. Though success rates are very good with Donor Egg IVF, many patients do not find this option attractive because the child will not have a genetic link to the mother. Freezing one’s own eggs at a younger age for use later in life can provide another option in addressing age-related infertility.

The Science behind Personal Egg Banking:
How does it work?

Until recently, egg freezing was an experimental procedure with limited success in only a few select programs around the world. However, the use of a specific type of freezing called vitrification, has led to a dramatic improvement in oocyte survival, fertilization rates, and pregnancy rates. Most importantly, these successes are being reported by many different centers worldwide.

Based on the reports of approximately 1,000 births worldwide through egg freezing and our own successes at GIVF, we now offer Personal Egg Banking to women as a means of improving their chances of conception if they plan to delay childbearing. The experience so far with frozen eggs predicts that a patient in her 40s would significantly improve her chances of a successful pregnancy if she were able to use eggs that were frozen at a younger age (e.g. 30s).

Who is a candidate for Personal Egg Banking?

Not every woman is a good candidate for egg freezing. Women who are over 40 years of age or already have significantly decreased ovarian reserve (poor egg quality) may not benefit from egg freezing. Additionally, younger women (under age 30) need to carefully consider whether freezing eggs will be of later benefit to them. These women are more likely to conceive without assistance as they have many more years to conceive without assistance.

A major part of offering Personal Egg Banking to women is appropriate counseling. Key points to consider include:

1) Egg freezing requires ovarian stimulation and egg retrieval. Multiple mature eggs must be retrieved to have a realistic chance of conception after freezing and thawing. In a natural menstrual cycle, only one egg is matured each month. Therefore, patients who choose egg freezing are given medications to stimulate the maturation of multiple eggs in a single cycle (same treatment used for IVF patients). To appropriately time the egg retrieval, frequent office visits are required for blood tests and transvaginal ultrasound to monitor the development of the eggs. The eggs are retrieved by placing a needle through the back of the vagina into the ovary. This is an outpatient procedure performed in the office under anesthesia.

2) Freezing eggs is not a guarantee of future pregnancy and is still an emerging technology. Since egg freezing is an emerging technology, it is difficult to accurately assess the chance for pregnancy and delivery. Based on published data, largely from donor egg cycles, it is estimated that a single egg that is warmed from the vitrification method has a 4% chance of resulting in a live birth. These rates may be lower in women over the age of 32 since fertility is known to decline with advancing age and age is not the only determinant of egg quality. More recent reports and our own current experience suggest live birth rates will improve as techniques and protocols are refined, but are expected to remain low due to the inherent limited potential of a single egg producing a successful birth. As with all pregnancies, naturally or assisted, there is no guarantee of a normal outcome.

If you would like to receive information about Personal Egg Banking, click here.

Clinic Offers Single IVF Cycle Pregnancy Guarantee

The Genetics & IVF Institute (GIVF) in Fairfax, Virginia (in the Washington, DC suburbs) is offering a limited time Single IVF Cycle Pregnancy Guarantee. If you do not become pregnant after one IVF cycle you receive a full refund. The base cycle fee is $10,900 and medications are excluded from the refund. Some medical eligibility apply and patients must be 36 years old or younger when treatment begins. Offer is good through May 31, 2010. Click here to schedule an appointment.