THE ELEVATOR TO THE THIRD FLOOR OF 700 UNIVERSITY Avenue in Toronto opens to a panorama of activity. Large bellied women waddle to appointments; technicians call out numbers for blood work; health, credit and hospital cards are pulled out and stuffed back into pockets. The walls are cluttered with information — pamphlets,posters, ads for three-dimensional ultrasounds, research volunteers and breastfeeding help. Underneath a sign reading “Reproductive Biology Unit,”it’s standing room only.
This is where people like Stephanie (not her real name) are waiting.She spent more than half her life trying not to get pregnant as she powered through university, law school,and on to Bay Street as a corporate lawyer.She was married at 36 — a perfectly reasonable time to start thinking about having a family — so she thought.The reality was that throwing birth control out the window and waiting for the magic blue line on the pregnancy test turned into a three-year journey — much of it spent on this third floor which houses the obstetrics and gynaecology department for Mount Sinai Hospital and where University of Toronto researchers, clinicians and students use the latest diagnostic and therapeutic techniques available in Canada to treat infertility.Here is where she’s spent her time undergoing a litany of blood tests, ultrasounds,sperm washes and drug injections — not to mention her savings — before she and her husband were given the news — just shy of her 40th birthday — that she was pregnant.
She’s one of the lucky ones.
TICK-TOCK GOES THE CLOCK
It is estimated that one in six Canadian couples are infertile — unable to conceive a child after one year or more of trying naturally. And as women delay starting families, these numbers are rising. “There’s no secret, infertility is closely related to the increasing age of the mother,” says Dr. Ellen Greenblatt, associate professor of medicine, who specializes in obstetrics and gynaecology. She also has a sub-specialty in reproductive endocrinology, treating infertility as well as reproductive disorders that affect children,women and men,such as early puberty and early or late menopause.But for those who see her for fertility issues — and they make up the majority of her patients — the number one cause of their inability to conceive is related to the age of the woman. “The incidence of infertility increases dramatically after age 35. Even for women who use assisted reproductive technology, the fact is that embryo quality is affected by the woman’s age. Period.”
Greenblatt says that many women have a false view of their fertility.They hear about people having babies well into their forties — many of them celebrities. “On the celebrity end, many of these people do not share all of their information. It’s very likely that they are using donor eggs, for example.What normal,everyday women must remember is that you can’t just assume your fertility will be there when you want it.”Greenblatt points to falsehoods and old wives’ tales about fertility.“There’s a false sense that you can delay your fertility because you’re on the pill,or that if you are healthy in general,you won’t have fertility issues.”As a result,Greenblatt says, fertility education has to start early.She wants to get the message to primary caregivers and physicians that they must educate their young female patients about the fertility window.
Female infertility increases with age. One in 7 women aged 30 to 34 are infertile. A quarter of women aged 40 to 44 cannot conceive.
Stephanie and others in her age group are well aware of the window, the proverbial biological clock ticking louder with each birthday, but for most women,it’s not a factor that will make them alter their lives dramatically while in their fertile prime.“The last thing that was on my mind while I was in my 20s was having children,” says Stephanie.“I was going to school, building a career,and besides,I wasn’t in the kind of relationship where starting a family was even an option.You can’t force yourself into becoming family minded when your social or economic reality is so far the other way.”
This demographic reality has left many women with no choice but to wait and see if their fertility is there when they want it,and hope to beat the odds even when they’re not in their favour.Helping them play those odds are hospital centres like Mount Sinai’s,as well as private clinics.The Toronto Centre for Advanced Reproductive Therapies (TCART) is one such place. Housed high above the designer boutiques and tony patios of Toronto’s fashionableYorkville neighbourhood,TCART provides hope for women who covet a baby.
Bob Casper,TCART’s director, is a professor of obstetrics and gynaecology at U of T and a senior scientist at Mount Sinai’s Samuel Lunenfeld Research Institute. Although his clinic specializes in maximizing positive outcomes for pregnancy,Casper doesn’t mince words when he says that the odds of having a baby are clearly stackedagainst older women trying to conceive and admits that the cost of that hope — emotionally, financially and socially — is tremendous. “We counsel patients on all aspects of the process,noting that while we use the most advanced techniques vailable,there is no guarantee.”
Casper, an internationally-renowned infertility specialist, describes the basic infertility investigation as threefold: First, a check is performed to see if a woman is ovulating or not. Anovulation, or failure to ovulate, is responsible for about 30 per cent of all infertility cases. Second, an ultrasound is performed to see if the fallopian tubes are open so that the sperm and eggs can get together.Tubal and/or adhesive issues (which prevent fertilization) account for 35 per cent of all cases. Finally, a man’s semen is tested to see if his sperm count and motility (its ability to move independently) is normal.This “male factor” is the sole cause of infertility in about 20 per cent of couples and contributes to infertility in a further 30 to 40 per cent of cases.Finally,about 10 per cent of infertility cases are unexplained.
If ovulation is the issue,medication to stimulate ovulation is prescribed.Casper and his colleagues have developed a new medication — an aromatase inhibitor — that has significantly fewer side effects than the medication clomiphene citrate that has been used for 40 years. Clomiphene citrate can make the lining of the uterus too thin for an embryo to implant.“We’re able to overcome those problems by utilizing a drug that is presently on the market for treating women with advanced breast cancer,” says Casper.“While it’s not yet approved in Canada,there are FDA-approved clinical trials going on in the United States in the hope of showing that aromatase inhibitors are superior to clomiphene citrate,with fewer side effects and better pregnancy rates.”
If six cycles on an ovulation stimulator pass with no results,a patient may undergo intrauterine insemination (IUI),when washed sperm (sperm that has been removed from semen) is inseminated by a small catheter into the uterus through the cervix.When this is not successful, or if the issue is tubal blockage, male factor or a combination of the three, in-vitro fertilization is offered.
Sperm Damage
Bob Casper and his colleagues developed the first test to assess DNA damage in sperm and have shown, for example, that cigarette smoking results in increased DNA damage.They’ve also found a plant anti-fungal chemical, resveratrol, that may actually repair this damage. It also holds promise to slow DNA damage in lungs and may be useful in the treatment of pre-cancerous lesions in lungs.
A Good Egg
Women are born with all the eggs they will ever have, and as they age, their quality is diminished. Bob Casper of TCART and Dr.Andrea Jurisicova, assistant professor of Obstetrics and Gynaecology and the Canada Research Chair in Molecular Reproduction are trying to find a way to improve the quality of those eggs.Before conception, eggs are in a resting state and they have 46 chromosomes. To conceive, an egg needs to rid itself of half of those chromosomes in order to meet the sperm’s 23 chromosomes and form a perfect embryo. However,over time, the eggs lose the energy required to perform this task.The energy — produced by the mitochondria — fades, causing lethal damage to the embryo.Most of these embryos don’t survive, causing miscarriage. Those that are born are largely cases of trisomy 21 (an extra chromosome that the egg could not rid itself of during conception), or Down’s Syndrome. Jurisicova is trying to find a way to refresh the mitochondria, so that it retains the energy required at conception.Jurisicova is also investigating the underlying genetic associations to female infertility — an area that has not been studied previously.This is in stark contrast to male infertility,where scientists have already identified several genes linked to sterility.
TEST TUBE BABIES
Although in-vitro fertilization (IVF) has been around since 1978, it is still considered a high-tech fertility treatment, and comprises the majority of TCART’s activity. IVF involves getting eggs from the woman and sperm from the man and creating embryos in a dish and then putting them back in the woman. As Casper explains, IVF was developed to bypass tubal blockage problems but there are a lot of other reasons to undergo the procedure.One is for very low sperm counts.“With IVF we can get babies for couples who, in the past, used donor sperm because the sperm count was too low.” There is also the more advanced intra-cytoplasmic sperm injection (ICSI),where doctors literally hold the egg and inject it with the sperm, place it into a dish and let it fertilize. ICSI has been around since 1994 and has been a real boon in treating male factor infertility.Technologically, ICSI is at the cutting-edge of assisted reproduction: The TCART embryologists use a needle the size of a red blood cell, under a microscope, and with the assistance of hydraulics, fertilize an egg.
Part of Casper’s research focuses on endometriosis — a condition in which the lining of the uterus prevents the embryo from implanting properly.“IVF bypasses that and most other adverse environments in the abdomen nicely.” For Stephanie and others like her, IVF is not as easy as it sounds.The fertility investigation can take months, with cycle monitoring and repeated rounds of clomiphene citrate producing no pregnancy.As time goes by,the woman’s age increases,causing added stress.For Stephanie,whose positive outcome eventually happened on round two of IVF, “I wish we could have just jumped straight to IVF, I would have saved a few years.But I know it doesn’t work that way.”
BABIES COST BUCKS
Popular literature says the cost of raising a child from ‘crib to college’ is somewhere in the range of $200,000 to $300,0000. If that’s true, Stephanie’s already spent 10 per cent of that and her baby is not even born yet. Despite her company’s generous drug plan, she estimates that drug treatment and IVF has cost her about $28,000.
“I’m lucky I had the means to undergo this,”she says, adding that her savings and family support allowed her and her husband to pay the astronomical costs associated with assisted reproduction.“It is not easy,but we were able to find the money for this. I can’t imagine that this treatment could even be an option for people of lesser means.”
According to Greenblatt,it’s not.“IVF and many assisted reproductive technologies are bizarre in their costs,and this is where the Canada Health Act really does not hold true. IVF costs are determined province by province.And in Ontario,it is very complicated. For women with blocked fallopian tubes,the professional fees for IVF are covered by OHIP, and the non-professional portion (the costs on top of the doctor’s fee) is covered only when you are in a funded program like ours. In short, there is a very large amount of the cost that is not covered — into the thousands of dollars.”In Ontario, the only four funded clinics (that pay a portion of the non-professional IVF costs for blocked fallopian tubes) are at Mount Sinai Hospital in Toronto,as well as in Ottawa,Hamilton and London.
Price Check
In Vetro Fertilization
| Semen Assessment or IVF- each sample |
$350 |
| IVF Cycle Fee (delisted) |
$7,500 |
| Refund if no egg retrieval |
$2,750 |
Embryology Fee
(OHIP patients only) |
$1,500 |
| Intracytoplasmic Sperm Injection (ICSI) |
$1,200 |
| Sperm Extraction Procedure
Urologist Fee, payable at Urology Clinic |
$750 |
| Sperm Wash Conversions to IVF |
$2,800 |
| Processing Fee for Frozen Sperm
(each sample) |
$250 |
| Processing Fee for Partner's Short Term
Frozen Sperm (each sample) |
$250 |
| Processing Fee for Retrograde Sperm |
$250 |
| Mock Cycle / Monitoring |
$700 |
ARTIFICIAL INSEMINATION
| Semen Assessment for IUI- each sample |
$350 |
| Processing Fee for Frozen / Fresh / Donor
Sperm per IUI |
$300 |
| Ovulation Prediction Kit |
$40 |
| Ovulation Sticks (each) |
$10 |
| Progesterone Suppositories (ea) |
$2.50 |
| Annual Storage Fee |
$240 |
SPERM BANK
| Initial Semen Processing and Freezing
(Including 1 year storage) |
$300 |
| Repeat Semen Processing and Freezing |
$150 |
| Sperm Preparation Fee (intrauterine
insemination) each sample |
$300 |
| Annual Storage Fee |
$240 |
SURROGATE AND DONOR PROGRAM
| Medical Assessment |
$700 |
| Sonohysterogram |
$100 |
| IVF Cycle |
$5,800 |
| Refund if no egg retrieval |
$2,900 |
| Embryo Donation |
$2,500 |
| Refund if no embryo transfer |
$300 |
| Progesterone Suppositories (each) |
$2.50 |
| Annual Storage Fee |
$240 |
EMBRYO FREEZING AND TRANSFER
| Embryo Freezing including year 1 storage |
$650 |
| Embryo Thawing and Transfer |
$1,100 |
| Annual Storage Fee |
$240 |
In some private clinics like TCART,OHIP coverage is also accepted for women with blocked tubes,except for a small portion of the cost,which is the clinic overhead.Other clinics expect full payment whether the infertility is caused by blocked tubes or not.“And then everybody else is out of luck,”says Greenblatt.“All other indications for infertility other than fallopian tube blockage — which usually amount to about 85 per cent of couples — are not covered. Even for those with drug plans, it is variable as to which plans will cover the infertility drugs.”To counter this cost, some patients have enrolled in programs where they buy leftover drugs from women who have finished treatment.
As a former National Director of the Canadian Fertility and Andrology Society and a board member of the Infertility Awareness Network,Greenblatt is involved with lobbying provincial governments to consider covering the cost of fertility treatment more broadly.“There is a very relevant argument here,” she says, explaining that because of the prohibitive cost of fertility treatment, women are pushing to have more than one embryo implanted into them at the time of IVF or ICSI.The problem is that this results in multiple pregnancies,which cost the entire health system an enormous amount of money. “It is a simple mathematical fact.Multiple births cause the system a lot of money. If the government could fund IVF, it would be an excellent trade off.”
THE DEEP FREEZE
Advances in the field of assisted reproduction are not always about immediate pregnancy.Greenblatt, for example, counsels many women interested in preserving their fertility before they undergo treatment for cancer.“These women have been given the devastating diagnosis of cancer, and then told,‘and by the way,you may be left infertile as a result of the treatment’,” she says.“Thankfully,we can do something about this by freezing women’s eggs or fertilized, mature embryos so that they are available after their treatment.Men have been doing this for years with the use of sperm banks and now we’re able to do this with women.” This practice, though common and accessible, is prohibitive by cost. Greenblatt wistfully shakes her head, when asked if this treatment is covered, repeating, “No, OHIP only covers treatment for blocked fallopian tubes — 35 per cent of all cases.”
WOMBS FOR RENT
We’ve all heard the tabloid stories about the surrogate mothers who bear children using various permutations and combinations of donor sperm, eggs and a woman who will eventually be or not be the baby’s legal mother.
In Canada, this is called using a “gestational carrier” and it is perfectly legal, as long as it is done for altruistic reasons. A woman cannot donate her eggs or her body to carry an embryo to term for financial gain.At private clinics and hospital centres, there is a significant counseling aspect to this activity.At TCART, for example,counseling aims at making sure the gestational carrier is not being pressured.“ If these women feel a sense of obligation, it may not be the best arrangement,” says Casper. At Mount Sinai and TCART,many families use donor sperm to conceive,and this is the most popular way that women in same-sex relationships have children.
BABY MAKING:WHEN TO STOP?
As research advances in the field of assisted reproductive technology, the opportunities for couples to have families, despite their odds, has risen.Yet at what point does a couple stop trying to conceive? Greenblatt and Casper agree that it is largely a personal choice, and often the financial costs of one unsuccessful cycle after another make the decision for these couples.At Mount Sinai and TCART,psychologists and social workers help individuals and couples grapple with these issues.“Unfortunately, even with IVF,each cycle is independent of the others — it’s like flipping a coin, there is no guarantee that pregnancy will occur.We are improving the environment in which you can take those chances, but still, it is chance.” Undergoing fertility treatment — even if successful — can cause tremendous strain on a couple’s relationship, adds Greenblatt.There is the treatment itself, not to mention the loss of privacy and modesty that fertility treatment necessitates.“Suddenly a very private part of a couple’s life becomes a very clinical,matter-of-fact,activity.”
For Stephanie and her husband, they are not sure when they would have stopped.“The treatment itself is not easy; it’s invasive, it requires modesty to take a back seat to your goal of becoming pregnant and it takes a lot of financial and emotional resources.”As for future children, Stephanie has chosen to freeze the extra embryos that were produced through the IVF process and hopes that if she and her husband decide, they can have them reimplanted for another child.They know that will be an additional round of medical procedures, and additional, significant costs.But for now, she is happy that she, like many others,has beaten the odds thanks to research, science, a little luck and a lot of money.
Thanks to Dr.Ted Brown,Division Head, Division of Reproductive Endocrinology and Infertility,Department of Obstetrics and Gynaecology, Faculty of Medicine, for his assistance with this story.