Feature / Summer 2010
Parents – At Last!

Reproductive science has made huge strides over the past 30 years, bringing hope to millions of infertile couples. But some formidable barriers remain


Illustration by Adam Simpson

Young, healthy and in love, Lynne and David Stawicki* were eager to start what they hoped would be a large family. A year passed, then another. By the third year without a pregnancy, the couple nervously sought medical testing. The results stunned them: David’s sperm sample proved to contain no sperm at all. Zero. “I was shocked,” says David, 34.

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Further tests revealed the reason: David was born missing both vas deferens, the two tubes that ferry sperm from the epididymis, behind the testicles, to the ejaculatory ducts. Genetic testing found that he was a carrier of cystic fibrosis, a chronic – often fatal – disease of the lungs and digestive system. While David didn’t have the illness or any apparent symptoms of it, the lack of vas deferens (causing certain infertility) is common to all men who have the disease. “He had sperm,” says Lynne, 32, “but no way for it to get where it needed to go.”

Toronto Fertility Clinics

Doctors mentioned in this article are affiliated with the following fertility clinics:

The Stawickis’ doctor referred them to Dr. Keith Jarvi, a urologist specializing in male infertility and a professor of surgery at U of T. Toronto was a distant 1,400 kilometres from the couple’s northern Ontario home, but it was their best hope. As Jarvi says, “There’s a huge infertility infrastructure here, and Toronto is a world leader in cystic fibrosis and male infertility research.” In a precisely synchronized series of procedures, doctors used a syringe to extract sperm directly from David’s testes; they then retrieved mature eggs from Lynne’s ovaries. Several days after the eggs were successfully fertilized in a Petri dish, two embryos were transferred to Lynne’s uterus. The couple are now the parents of healthy 16-month-old twin boys. “It’s pretty amazing,” says David. “We know how fortunate we were to get that referral.”

Toronto has one of the country’s highest concentrations of infertility experts, and many of them are associated with U of T. The university’s division of reproductive endocrinology and infertility, in the department of obstetrics and gynecology, includes 15 infertility specialists, three basic scientists, four reproductive endocrinologists and a clinical embryologist. Many of these men and women also run fertility clinics in Toronto and engage in various strands of research that investigate the causes, diagnoses and treatments of infertility – a disturbingly common condition that afflicts 10 to 20 per cent of Canadian couples, or approximately one in six.

Because infertility was scarcely talked about a generation or two ago, we don’t know if the problem is becoming worse, and, if so, how much worse. But Ted Brown, the division’s academic head and a professor in obstetrics and gynecology and physiology, says, “It seems to be increasing. Couples are waiting longer to have children, as careers take time to become established, and fertility declines with age.”

But there’s a host of other reasons that people can’t produce or sustain a pregnancy. The causes can be structural, such as absent, blocked or deformed Fallopian tubes, uterus or vas deferens; or hormonal, including thyroid or sex hormone imbalances. They can be genetic, causing chromosomal aberrations in the egg, sperm or embryo; or the result of infections, such as from sexually transmitted diseases, which produce inflammation or scarring. Exposure to smoke, excessive alcohol, toxins, extreme stress or, in men, excessive heat to the genitals, such as that experienced by chefs or long-distance cyclists, are also factors. Then there’s the most frustrating reason of all: undetermined. While infertility problems have traditionally been blamed on the woman, in fact men may account for up to 50 per cent of the problem, says Brown.

But if infertility is on the increase, so is the range of treatments available, thanks in part to the work of many U of T–affiliated clinicians and researchers. Last year Mount Sinai Hospital consolidated its fertility programs into a new multidisciplinary, state-of-the-art facility. One of the centre’s many features is a quarantined lab for infertile couples in which one partner has a viral infection such as hepatitis B or C or HIV-AIDS. “Although the centre is a hospital program, it’s a soothing, off-site environment, so we have the best of both worlds,” says medical director Dr. Ellen Greenblatt, a professor in obstetrics and gynecology at U of T. Patients seeking help for infertility aren’t required to share waiting rooms with pregnant patients. The centre has about 18,000 clinic visits a year.

One common infertility problem is recurrent early miscarriage. That’s a particular area of interest for Dr. Sony Sierra, co-founder of First Steps Fertility clinic and a professor at U of T in obstetrics and gynecology. Almost half of all pregnancies miscarry before six weeks, Sierra says, chiefly because of random genetic error. But when a woman miscarries three pregnancies in a row, there’s often another reason. And sometimes the treatment can be surprisingly low-tech.

Case in point: Chloe Prasad,* a university professor herself, sought help from Sierra during her second pregnancy, which, like her first, ended in miscarriage. The 35-year-old was quickly diagnosed with polycystic ovarian syndrome, a common endocrine disorder affecting about seven per cent of infertile women and linked to diabetes. “I felt in perfect health, but I did have irregular periods and there is diabetes in my family,” Prasad says. After Prasad’s second miscarriage, Sierra put her on a course of metformin, a diabetes drug to help regulate insulin levels. “It worked like a charm,” Prasad says. “My husband and I have a beautiful, perfect, healthy son born last year.” She recently underwent another course of metformin and is pregnant again, due this fall.

While recurrent early miscarriage often has a physical or hormonal cause, Sierra says that something as simple as regular ultrasounds may help overcome some of these obstacles. A 2006 study (for which Sierra was a co-author) of 1,800 couples who had experienced at least two miscarriages found that simply by giving the patient two additional, reassuring ultrasounds in the course of a pregnancy increased the rate for successful completion from 15 per cent to 71 per cent, without the help of in vitro fertilization (IVF) or any other reproductive technology. “The mind-body connection is powerful, and psychological stress plays a huge role,” Sierra says. Using highly complex microarray technology, she is also conducting research into what she calls the “black box of pregnancy” – the two weeks after a woman releases an egg – to investigate exactly what happens to the endometrial lining to make it receptive or hostile to implantation.

There’s also a growing emphasis on preserving fertility in people who are at risk of losing it, such as cancer patients. Chemotherapy, radiation and surgery can compromise fertility, sometimes permanently, by damaging delicate testicular cells and some cell DNA. Dr. Kirk Lo, a urologist, a professor in the department of surgery at U of T and a surgeon investigator at Mount Sinai, sees boys and young men in their teens, 20s and 30s before cancer treatment to discuss options. The easiest is to take a few sperm samples – either through ejaculation or extraction – and freeze them, a process that leaves sperm viable for at least 20 years. But Lo says up to half of all oncologists don’t even discuss the issue with their young male patients or families. “Sperm preservation is not difficult, but awareness is a major issue, both among health professionals and the general public,” Lo says. He’d like every cancer centre to have one staff member specializing in fertility issues.

Taking the issue a step further, Lo’s lab is investigating ways to protect sperm cells from chemotherapy damage, even in males too young to produce sperm. Lo has been able to remove testicular stem cells from cancerous mice before chemotherapy and then inject them back afterward, restoring fertility. The way of the future, he suggests, will be to take stem cells from skin and reprogram them to become sperm cells. Lo and colleague Jarvi are also world leaders in identifying the more than 2,000 different proteins in semen, some of which may be markers for everything from infertility to prostate cancer.

Preserving fertility in females is a greater challenge. Extracting an egg for freezing can require weeks of preparation, and cancer patients often don’t have the luxury of time. Teresa Lee* was 25 when she developed non-Hodgkin’s lymphoma, a cancer of the lymphatic system. There was such an emphasis on saving her life that there was no time or opportunity to extract and freeze her eggs. Lee is now 28 and healthy again, but has a lower “ovarian reserve.” She and her husband have gone through three cycles of IVF, with no pregnancy. While drugs to help protect ovaries during chemotherapy are still experimental, Lee urges women to investigate their options. “You don’t realize how important fertility is until it’s taken away from you,” she says.

Infertile couples who do undergo successful IVF treatments often have another challenge to deal with: multiple pregnancy. To ensure that at least one embryo will “take,” IVF specialists often transfer two into a patient simultaneously (or more, as in the case of California’s “Octomom,” who gave birth to eight babies last year). Couples who have struggled to have a baby may think that multiples will be a bonus. But almost half of all twins and 90 per cent of all triplets, quads and quints are born premature, and multiples are five times more likely than single babies to have birth defects and disabilities.

A hot area of research is therefore the quest for the “best” egg to fertilize or the “best” embryo to transfer – which is tricky, considering that at least half of the eggs of an average, healthy young woman are abnormal. Dr. Robert Casper, professor of obstetrics and gynecology and medical director of the Toronto Centre for Advanced Reproductive Technology, is working on developing a quick, inexpensive test for egg selection. Since a healthy egg when it matures casts off half of its 46 chromosomes into an outlying structure called a polar body, a test that finds more or fewer than 23 castoffs in the polar body would suggest that the egg may be abnormal and therefore not a good choice for IVF. “If we can select which embryos to put back, it would allow us to put back fewer,” Casper says.

Casper adds that while the eggs of a woman in her late 20s or early 30s are optimal, by the mid-30s the eggs don’t always have the energy to separate their chromosomes properly. His lab has been working on reversing that process in mice by treating them with the naturally occurring compound co-enzyme Q10, which revs up mitochondria, the cell’s “batteries.” He says, “We were quite surprised that the eggs of these animals, who were 52 weeks old, looked 10 weeks old again.” He’s begun a randomized clinical trial in women over 35, with results expected next year. More than a decade ago, Casper and his team were the first to use aromatase inhibitors, drugs that block estrogen, instead of clomiphene to induce ovulation. Now standard therapy in many clinics, aromatase inhibitors are as effective as the older drug, but with fewer side effects to mother and baby.

Future research on infertility will almost certainly include more studies to find genetic links and identify molecular pathways of development for eggs, sperm and embryos. “I’m really interested in trying to identify what factors are required for embryo development and why some embryos grow slowly or fragment,” says Andrea Jurisicova, a scientist at Mount Sinai and a professor in obstetrics and gynecology and physiology at U of T. Jurisicova, whose lab works on egg cells from mice, says she’s excited that our increasing knowledge of genetics will vastly improve our understanding of infertility.

Meanwhile, Jurisicova has shown just how fragile fertility can be. In 2007 she headed a study that found that female mice exposed to the environmental pollutants called polycyclic aromatic hydrocarbons, even before they got pregnant, dramatically reduced fertility in their offspring. The chemical, found in cigarette smoke, car exhaust, charred and smoked food, and fumes from wood stoves, caused a two-thirds drop in the number of egg-producing follicles in their female offspring. Fewer eggs mean lower fertility and earlier menopause.

“There may be a message here for young girls who are thinking about starting to smoke,” Jurisicova says. “It’s possible that the impact of these chemicals on fertility could be much more long term than people think.”

*The names of couples seeking infertility treatment have been changed.


Reader Comments

# 1
Posted by Scott Anderson on July 7th, 2010 @ 3:23 pm

I noticed that the cover illustration for the article “Parents – at Last!” included no queer families. I hope that, in the future, U of T Magazine can take a more inclusive perspective, especially when dealing with an issue that affects basically all queer families.

Zach Witte
Rotman Commerce Pride Alliance
Toronto

# 2
Posted by Scott Anderson on July 15th, 2010 @ 11:42 am

Perhaps the title of this article should be “Science gives new chances to rich infertile couples.”

Science has helped increase the chances of an ‘infertile couple’ conceiving – for the lucky few that can afford the procedures. IVF is prohibitively expensive to the “average couple” and has a success rate of less than 35%, which means that a couple may drain their savings, go into debt and pour all their hopes into something that will never happen. Only a select few can afford more than one IVF procedure. None of the fertility procedures (sperm wash, intrauterine insemination, IVF, etc) are covered by the government and most insurance companies do not cover any fertility drugs, let alone IVF.

As well as being monetarily draining, trying to have a baby is emotionally draining – especially for women. Reproductive medicine is important but so is mental health. I suspect there are significantly more women dealing with the emotional repercussions of miscarriage and infertility than experiencing the miracle of pregnancy through IVF. Women who are depressed are reticent to try anti-depressants because of the possible effects on the child. I would like to see someone expose the other side – the have-nots instead of the haves; the couples who have exhausted their bank accounts; those who can’t afford reproductive technology; the women who have been fruitlessly poked and prodded with daily ultrasounds and needles; those who are emotionally spent.

It is easy to glamourize the wonders of science; more difficult to tackle the reality of most infertile couples.

S. Hunter

# 3
Posted by Scott Anderson on August 25th, 2010 @ 4:28 pm

I was exceedingly concerned by the lack of appropriate information provided in this article. Yes, biology and time unfortunately do play havoc on women’s fertility. However not every woman chooses to start a family late in life. Some women have to deal with unforeseen circumstances. Life happens as you’re planning it. Does that mean that you should be denied a family because of events you cannot control?

Perhaps researchers should look into how to preserve and extend a woman’s fertility naturally (this does not mean using donor eggs) and improving fertility meds to make them less toxic. These would help save many women much unnecessary anguish.

Yes, fertility treatments should be covered by OHIP and other provincial health plans. I don’t think that people wake up in the morning and decide that they want to be infertile. Also, not everyone who seeks fertility treatment is wealthy. Unfortunately the astronomical fees that are attached to fertility treatments deter people who are not well off from seeking treatment. Are the poor not entitled to fulfilling their dreams of having a family?

Lisa Frasca
BA !998 Victoria
Toronto

# 4
Posted by Scott Anderson on September 3rd, 2010 @ 3:43 pm

The parting shot in this article highlights the palpable and severe effects of common environmental pollutants, such as cigarette smoke, on couples trying to conceive. The reproductive hazards of cigarette smoking are well established and have been linked with decreased fertility in both smokers and those exposed to second-hand smoke. Recent research from McMaster University has shown significantly higher levels of benzo[a]pyrene (B[a]P), a constituent of cigarette smoke, in the follicular fluid of women who did not conceive, as compared to those who achieved a pregnancy. Furthermore, women exposed to mainstream smoke were found to have significantly higher levels of B[a]P in their follicular fluid, as compared to their side stream-exposed or non-smoking counterparts.

The important finding that B[a]P reaches the follicular fluid and the fact that it is found at much higher levels in women who smoke provide further evidence that, of the many toxicants present in cigarette smoke, B[a]P may be an instrumental compound in the adverse effects of cigarette smoke on follicular development and subsequent fertility. This, coupled with the fact that more women are smoking and taking up the habit at younger age, will have reproductive consequences by shortening and compromising their reproductive lifespan.

Michael S. Neal
Scientific Director, ONE Fertility
Burlington, Ontario

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