Exclusive: Meet the World’s First Baby Born With an Assist from Stem Cell

Doctors in Canada have begun a new chapter in medical history, delivering the first in a wave of babies expected to be born this summer through a technique that some experts think can dramatically improve the success rate of in vitro fertilization (IVF).

Now 22 days old, Zain Rajani was born through a new method that relies on the discovery that women have, in their own ovaries, a possible solution to infertility caused by poor egg quality. Pristine stem cells of healthy, yet-to-be developed eggs that can help make a woman’s older eggs act young again. Unlike other kinds of stem cells, which have the ability to develop into any kind of cell in the body, including cancerous ones, these precursor cells can only form eggs.

In May 2014, Zain’s mother, Natasha Rajani, now 34, had a small sliver of her ovarian tissue removed in a quick laproscopic procedure at First Steps Fertility in Toronto, Canada, where she lives. Scientists from OvaScience, the fertility company that is providing Augment, then identified and removed the egg stem cells and purified them to extract their mitochondria.

Mitochondria are the powerhouses of the cell, a molecular battery that energizes everything a cell does. Adding the mitochondria from these egg precursor cells to Natasha’s poor-quality eggs and her husband Omar’s sperm dramatically improved their IVF results. In the Rajanis’ first traditional-IVF attempt, Natasha produced 15 eggs, but only four were fertilized—just one of those matured to the point were Natasha’s doctor felt comfortable transferring it. “I knew it wasn’t the best-quality embryo, but it was what she had,” says. Dr. Marjorie Dixon, of First Steps Fertility.

With Augment, the Rajanis produced four embryos, two of which have been frozen should the couple decide to have more children. Another one became baby Zain.

It’s not currently available in the U.S., since the Food and Drug Administration (FDA) considers the process of introducing mitochondria a form of gene therapy, which it regulates. So far, some three dozen women in four countries have tried the technique, and eight are currently pregnant. All of the women have had at least one unsuccessful cycle of IVF; some have had as many as seven.

“We could be on the cusp of something incredibly important,” says Dr. Owen Davis, president of the American Society of Reproductive Medicine (ASRM). “Something that is really going to pan out to be revolutionary.”

The Next Big Thing in IVF

The technique is indeed poised to usher in the next big advance in IVF; since the first baby, Louise Brown, was born using the process in 1978, the procedure has changed little. Scientists have made incremental advances in fine-tuning the procedure, but taken together, these improvements have nudged pregnancy rates upward by only a percent or two over the course of 35 years. As it stands, the IVF success rate is about 38% for women in their late 30s and 18% for those in their early 40s. Natasha’s first IVF cycle differed little from the one that produced Brown more than 35 years ago.

Augment emerged from a breakthrough made in 2004 by biologist Jonathan Tilly, then at Harvard Medical School and now chair of biology at Northeastern University. He found that cells scraped from the outer surface of the ovary contain the precursor cells that can provide a more reliable source of energy to older eggs. “The technique addresses a void now in IVF,” says Tilly. “No cell culture can circumvent poor egg quality or an egg that is simply too tired to execute what it is capable of doing. We are taking patients with a zero percent pregnancy rate, patients who have failed IVF because of poor egg quality, and getting them pregnant.”

The Rajanis had tried for four years to get pregnant, turning to fertility drugs, intrauterine insemination, and a naturopath before trying their first attempt at IVF. Natasha became pregnant once, but miscarried a few weeks later. “I tried to remain positive, thinking there is a light at the end of the tunnel, and that a baby will be there at the end,” she says of all the misses.

What finally made the difference wasthe population of her own egg stem cells. What makes these cells so enticing to scientists is that they come from the mother herself. Mitochondria contain their own DNA, and in a controversial decision the U.K. government recently approved so-called “three-person babies,” where mitochondrial DNA from a donor is introduced into the egg of a woman with mitochondrial disease. When the egg is then fertilized and results in a live birth, it can raise ethical questions, biological concerns and conflicts about parenthood.

With Augment, the cells used—and their mitochondrial genes—are from the mother’s own ovaries. Still, the FDA requested more studies on the effect of adding mitochondria, even from the mother who provides the egg, to the IVF process. OvaScience plans to conduct 1000 cycles using Augment this year, and generate more data that will help bring the procedure to the U.S.

Because the procedure is so new, some reproductive science experts are skeptical. What’s lacking, they say, is convincing evidence comparing pregnancy rates of women undergoing Augment to those with similar infertility problems who didn’t use the technique. So far, no formal clinical trials have been conducted; the only data on the procedure comes from recent presentations by Dr. Robert Casper of University of Toronto and Dr. Kutluk Oktay from Gen-ART IVF in Ankara, Turkey, both of whom are advisors to OvaScience.

“We’re not yet sure the scientific model has proven what the outcomes would be if you use the mitochondria of a younger egg, or from an egg stem cell,” says Davis of ASRM. “It’s a fascinating concept but we just haven’t seen the studies yet.”

In the world of infertility, however, such data are historically hard to come by. A lack of regulation of most reproductive technologies—the ones that don’t fall under the jurisdiction of the FDA as either drugs, devices or gene therapy—and the dominance of business-minded scientists has rushed new methods to clinics, often before their effectiveness has been fully proven.

Tilly counters doubters with evidence from other species that these cells can do what OvaScience has said they can. Egg precursor cells extracted from ovarian tissue from rats, mice, monkeys, pigs and women, for instance, have developed into immature eggs and, in the case of rats and mice, those eggs have mature and produced viable offspring. “Mitochondria from egg precursors rejuvenate the egg to bring it back to a high quality state,” says Tilly.

That appears to be the case with the Rajanis, and time will tell whether that ends up holding true for the other women trying Augment, too. “We see Zain as a symbol of hope for all couples struggling with infertility,” says Natasha. “While the process is long, emotional and physically draining, there is light at the end of the tunnel—and that light for us is Zain.”
http://time.com/

IVF doctors slam 65-year-old mum of quads Annegret Raunigk

FERTILITY experts have slammed a German mother-of-thirteen who went on to have IVF quadruplets at the age of 65, saying the case damages the reputation of artificial insemination.
“It’s the kind of tale which makes headlines around the world and skews the image of our field,” said Francoise Shenfield, a specialist in reproductive medicine and bioethics at University College London.

The controversy swirls around Annegret Raunigk, a Berlin teacher near retirement age who is the oldest woman to have given birth to quadruplets.

After going to Ukraine for in-vitro fertilisation from anonymous donors, Ms Raunigk gave birth last month to three boys and a girl, delivered by Caesarean about 15 weeks early.

The babies weighed between 655 and 960 grams at birth, but have since gained between 30 and 50 per cent in weight “and are developing well”, Berlin’s Charite Hospital said.
One is on respiratory assistance and the others “require milder aids for breathing”, it added, but medical confidentiality barred it from saying more.

One baby required surgery for an intestinal problem, doctors said last month.

Specialists interviewed at the annual conference of the European Society of Human Reproduction and Embryology, closing in Lisbon on Wednesday, highlighted ethical concerns about the mother’s age and risks for the babies.
There is no international regulation of fertility treatment and national guidelines are based on medical opinion.
A general age limit for IVF is about 50, close to the typical onset of menopause, the experts said.
Women in Germany today live to around 85, “so you could argue that a 65-year-old’s got 20 years and could see that child through to adult life”, said Adam Balen, a professor of reproductive medicine and chairman of the British Fertility Society.

A much bigger concern, he said, was that the clinic had implanted numerous embryos to boost chances of a live birth.
“Multiple pregnancies are dangerous. They’re dangerous for the mother, but they’re more dangerous for the babies,” he said.

Fertility clinics in advanced economies stopped routine transfers of multiple embryos about six years ago.

The evidence shows that babies born from such multiple transplants generally enter the world with lower birthweight and higher risk of ill health and cognitive difficulties.

Most Western watchdogs recommend single embryo transfers, which are now much more likely to succeed than a decade ago.

The German Society for Reproductive Medicine describes Ms Raunigk’s case as “extremely questionable”.

“Egg donation and especially the transfer of more than one embryo should not have been allowed or performed in these circumstances, both on medical and ethical and moral grounds,” it says.
Ms Raunigk is not the first woman to raise a storm about IVF ethics.

One prominent case was Carmen Bousada, a single Spanish woman who in 2006 had twin IVF boys at the age of 66, making her the oldest woman at the time to become a mother.

She later admitted she had lied about her age to doctors, telling them she was 55.
After becoming a campaigner for the rights of older women to experience motherhood, Ms Bousada died of cancer in 2009, leaving orphans aged two-and-a-half.

Another is Nadya Suleman, a 33-year-old Californian woman who was dubbed “Octomum” after giving birth to octuplets.
It later transpired she was a single mother of six other children under the age of eight.
http://www.news.com.au/

New surrogacy laws pass in SA

SURROGATES in South Australia will get access to increased financial assistance under new laws passed by state parliament.

THE changes will also create a surrogacy register and a framework for advertising to allow prospective parents to contact a surrogate more easily.

The bill was brought to parliament by Liberal John Dawkins, who said many parents had told him that difficulties finding a suitable surrogate had forced them to look overseas.
http://www.perthnow.com.au/

ART fact sheet, ESHRE

ART fact sheet (July 2014)

Background

One in six couples worldwide experience some form of infertility problem at least once during their reproductive lifetime. The current prevalence of infertility lasting for at least 12 months is estimated to be around 9% worldwide for women aged 20-44.

20-30% of infertility cases are explained by physiological causes in men, 20-35% by physiological causes in women, and 25-40% of cases are because of a problem in both partners. In 10-20% no cause is found. Infertility is also associated with lifestyle factors such as smoking, body-weight and stress. Increasing age in the female partner is one of the most common explanations today.

It is now estimated that more than 5 million babies have been born worldwide since the first IVF baby was born in 1978.
Most ART treatments take place in women aged between 30 and 39.


Cycles/treatments

Europe leads the world in ART, initiating approximately 55% of all reported ART cycles.
In 2011, the latest year for which figures are available, 588,629 treatment cycles were reported from 33 European countries. This compares globally (in 2011) with 151,923 cycles from the US and 66,347 cycles from Australia and New Zealand. The number of cycles performed in many developed countries has grown by 5-10% per annum over the last few years, but that growth is now showing signs of slowing.

In 2011 France (85,433 cycles), Germany (67,596), Italy (63,777), Russia (56,253), Spain (66,120) and the UK (59,807) were Europe's most active countries. In the Nordic countries, Sweden leads the table with 18,510 cycles, followed by Denmark (14,578).

The most active countries in the world are Japan and the USA.
Availability of ART

The Nordic countries and Belgium (but also Iceland and Slovenia) have the highest ART availability in terms of cycles per million population.
In Belgium, the Czech Republic, Denmark, Estonia, Iceland, Norway, Slovenia and Sweden more than 3.0% of all babies born were conceived by ART. By contrast the proportion in the USA - with 61,610 ART babies born - was estimated to be slightly more than 1% of total births.
Around 1.5 million ART cycles are performed each year worldwide, with an estimated 350,000 babies born.

Pregnancies and delivery rates

An analysis of world data for 2006 put average delivery rate from ART treatment at 20.5% per aspiration and 25.2% cumulative from a single started treatment cycle.

Large differences exist between countries in the number of embryos transferred and resulting multiple births. However, there is a consistent trend towards transfer of fewer embryos. The overall average number is 1.75 embryos per transfer.

In Europe the multiple delivery rate has declined steadily since 2000 from 26.9% to 19.4% in 2011 compared to a multiple delivery rate of 30% in the US (27.5% twin, 2.5% triplet or more deliveries).
Sweden has the lowest multiple delivery rate in the world. In 74.7% of all cases a single embryo was transferred.

In Europe in 2011 the mean pregnancy rate per embryo transfer was 33.2% after IVF, 31.6 % after ICSI, 23.4% after frozen embryo transfer and 47.5% after egg donation. Rates are higher in younger (<35 years) patients.
Treatments

The most common fertilisation (treatment) technique is ICSI. Overall, ICSI accounts for around two-thirds of all treatments worldwide, and conventional IVF around one-third. However, these proportions vary greatly between countries, even though outcome rates with each technique are comparable.

Success rates from frozen embryo transfer are increasing, as are the number of FER cycles. Vitrification, as an efficient cryopreservation technique, has improved the outcome of both embryo and oocyte freezing.

Ovarian hyperstimulation syndrome (OHSS) is a complication related to ART. In 2011 there were 1683 OHSS cases recorded in 28 out of 33 European countries reporting to ESHRE, making up 0.6% of cycles. Russia (520), Italy (189) and Spain (184) reported the highest number of patients with OHSS.
http://www.eshre.eu/

Surrogacy and Egg Donation in BioTexCom

Our doctors

Kovpak Vitaly - embryologist

"I realize that thousands of patients place their fates in my hands. It can be said I create infertile couples’ happiness and their future children. I always remember this fact and my great responsibility. Entering embryology unit, my working place, I understand that someone’s family and happiness now depends on me and my work. People come to us from around the world and usually they visit our clinic after numerous unsuccessful attempts and being in do-or-die condition.  Working in the laboratory, I select only the highest quality, healthy eggs and sperm. After in-vitro fertilization I carefully monitor embryos’ development. I visit laboratory even on my weekends and holidays. In my mind's eye I always tune in to a positive result. I use the most effective methods to achieve it. It’s incredible happiness when pregnancy test shows two strips - pregnant! Our team members are sincerely glad when it worked out very well, sometimes our managers even cry with happiness when receive positive results in complicated cases. One can say that we have mostly financial goals conducting such procedures, and positive result of the program positively works on clinics income. But, take my word for it, it’s not so. Over the years, members of our team have stuck together and we have cousinly affection for each infertile couple. People who come to us need a certain help and wait for good news from us. I, in turn, understand that great responsibility devolves on me and positive result mostly hinges on my work. I love my job in the BioTexCom center. Day by day, we improve our methods of work and treatment, discuss diagnoses and look for the most appropriate solutions, conduct experimental works and participant in international conferences and seminars. We give the good, happiness for childless couples from all over the world, and we proudly carry out this great mission.

Mozgova Elena - fertility specialist

Every day I communicate with infertile couples, who come to Ukraine from different countries. Germany, Italy, England, Spain, Switzerland and many others. They are all very different, they speak different languages ​​and are of different age. But they all have one common problem - infertility and inability to have own babies in a natural way. We have a unique solution of this global problem- surrogacy and egg donation. I have an individual way with each of our patients. We do not have same protocols and failed contracts. Basing upon the medical examination and test results, I advise patients the most appropriate program in order to achieve desired pregnancy. I have a child, and I clearly understand feelings of my patients. I always do my best to make infertile people finally feel this incredible feeling of parenthood. Many of our patients come to the clinic with kids just to express gratitude and show the result of our collective work - healthy, beautiful babies with happy parents. Some couples, after two -three years after the birth of their child (with the help of BioTexCom), come back again to conceive a second one. Reaching my workplace, entering office, I imaginatively always ask higher forces to help me realize this miracle of fertilization and successfully conduct the program. We help women who sometimes have lost hope to become happy mothers. With the help of our unique methods, women of any age, gain the happiness of motherhood and even give birth to healthy children using donor eggs. Working with infertility diagnose I am ruled by the European experience, introduce the latest technologies. Moreover I have a great friendly team of professionals and together we do well.

Christie again vetoes bill regulating surrogate parenting pacts in N.J.

TRENTON — For the second time in three years, Gov. Chris Christie has vetoed legislation that would create rules for people in New Jersey who wish to conceive a child through a surrogate known as a "gestational carrier," disappointing same-sex couples and adoption advocates.

The "New Jersey Gestational Carrier Act" would have clarified the law that already allows these arrangements as it applies to women who, unlike surrogates, have no biological link to the fetus because the egg belongs to another woman.

In his veto message late Monday night, Christie noted the legislature had sent him exactly the same bill he had vetoed in 2012 "rather than work with interested parties to address concerns raised during the initial debate." Opponents, such as New Jersey Right to Life and the League of American Families, argued the bill exploits women and treats children as a commodity.

None of the "significant ethical and moral concerns raised by a government-enforced system of agreements to procreate" have been addressed, according to the veto statement. "I take seriously the need to guard against any societal deprecation of the miracle of life."

Andrea Bowen, Executive Director for Garden State Equality, called the veto "a terrible outcome for families across New Jersey who need gestational surrogacy agreements to strengthen their families. We deplore what Governor Christie has done."

Donald Cofsky of Haddonfield, past president of the American Academy of Adoption Attorneys, who worked with the legislative sponsors in crafting the bill, said the governor doesn't seem to understand gestational carrier arrangements are already legal in New Jersey.

"All this act did was clarify everyone's responsibilities and make sure no child left no child in the lurch," Cofsky said. He could envision a situation in which intended parents walk away from a child born with a disability, leaving the carrier responsible. "The child will end up with the state and the taxpayers would foot the bill," he said.

The state has not updated its surrogacy law since the Baby M case in 1988, which defined the legal relationship between a surrogate using her egg and a husband who used his sperm to conceive a child.

"New Jersey is usually in the forefront on these issues, but is trailing behind," Cofsky said.

The bill (S2648) required the carrier to sign an agreement saying she would surrender the child immediately upon birth, and the intended parents' names, not the carrier's name, would appear on the birth certificate. Both intended parents and the gestational carrier would need to undergo a psychological evaluation and hire an attorney. The intended parents would be mandated to pay for the carrier's attorney and all of their pregnancy and postpartum medical expenses, according to the bill.
http://www.nj.com/

Couple who had twins tell of regret after embryo aborted in surrogacy

AN IRISH couple who had twins using a commercial surrogacy clinic in India have spoken of their "dilemma" and regrets that a viable embryo with a heartbeat was aborted to allow the birth of their twins.

Fiona Whyte and her partner Sean Malone travelled to India last year to start a family via surrogacy after five years of failed IVF treatment that cost €30,000. Fiona (52), works as an Inspector Manager for the Health Information and Quality Authority, and Sean (53), does contract work for Eircom.

The couple, from west Clare, who both have children from previous relationships,paid €25,000 to a clinic in Mumbai to facilitate the birth of twins -- a boy and a girl -- through an impoverished young surrogate.

Tonight an hour-long documentary will be screened on RTE detailing the couple's plight and that of surrogates living "hand-to-mouth" in India.

The film, which exposes the lack of regulation of IVF and surrogacy in Ireland, will reignite a heated debate about the status of embryos and parentage ahead of a landmark Supreme Court hearing on issues surrounding children born under surrogacy arrangements.

Ms Whyte and Mr Malone opted to implant three embryos fertilised with Mr Malone's sperm -- and eggs from a separate female donor in India -- into the surrogate's womb to boost their chances of a successful pregnancy.

As a result, the surrogate, who was paid just 20pc of the overall fee, was carrying triplets.
But one of the embryos was subjected to "foetal reduction", or termination, because the clinic does not allow surrogates to carry triplets.

The foetal reduction procedure was carried out when a radiologist "stops the heart of one of the babies", according to Dr Kaushal Kadam, founder of the Corion Clinic in Mumbai.

Ms Whyte and Mr Malone speak of the dilemma posed by the clinic's strict ban against triplets.
"We took a gamble, but we really, really wanted it to work and we felt we were increasing our chances by going for three (embryos)," said Ms Whyte.

"It was really on that basis that we went for it. We felt this was our last shot."
The couple also tell how twins Donal and Ruby, who were brought home to Ireland through a complex system of exit visas issued by the Indian authorities -- and emergency travel documents issued by the Irish Government -- are "stateless" because they have neither Indian nor Irish citizenship.

The film, 'Her Body, Our Babies' details the lack of regulation of surrogacy in Ireland and India, which has become the destination of choice for couples paying for commercial surrogacy. It airs weeks ahead of a hearing by a full, seven-judge Supreme Court of a landmark surrogacy action.

Last year, the High Court ruled that a genetic mother of twin girls -- born to the woman's sister who acted as surrogate -- could be named as their mother on their birth certificates.

But the Government, which has appeared twice before the European Court of Justice in 2013 in relation to surrogacy matters, has appealed the High Court ruling.

LAWS

Despite a 2005 report on assisted human reproduction (AHR), there are no laws in this country governing a range of sensitive reproductive issues such as surrogacy, IVF treatment and embryonic stem cells.

Hundreds of families with children born via surrogacy are in legal limbo as they seek clarity from the courts.

Justice Minister Alan Shatter is preparing a new Family Relationships and Children Bill that will address certain aspects of the law on surrogacy.

Both the Irish Human Rights Commission and the Equality Authority have secured permission from the Supreme Court to make arguments the appeal.

"The Irish Government needs to wake up and do something about it because it (commercial surrogacy) is happening," said solicitor Marion Campbell who has advised Irish couples engaged in overseas commercial surrogacies.

We've turned blind eye to this issue for far too long

IF you watch the documentary 'Her Body, Our Babies' on RTE tonight, you will most likely have mixed emotions about surrogacy.

You will be moved by the plight of a couple from west Clare who paid €30, 000 for five years of failed IVF treatment.

Desperate to have a family together (they separately have children from previous relationships), this couple embarks on a rollercoaster journey to India to find a young surrogate to carry their child.
Fiona Whyte and Sean Malone are aware that the young woman they choose through a commercial clinic in Mumbai -- there is an entire a menu of potential egg donors and surrogates -- is living in the depths of poverty.

The young surrogates explain, pitifully, how they are motivated to carry another couple's child to help pay for the cost of raising their own children.

Wherever you stand on the abortion spectrum, you will be deeply uncomfortable by the fact that a viable embryo with a beating heart is terminated because the Indian clinic does not allow its surrogates to carry triplets.

It is a dilemma that Fiona and Sean struggle with as part of their bid to have a child -- twins as it turns out -- through commercial surrogacy in a country that appears to provide little protection for some of its most vulnerable citizens.

No time to bond, the babies are swept away as surgeons attend to the birth mother who has performed her part of the €25,000 contract -- for 20pc of the fee.
After six weeks, exit visas are secured for the twins, who do not have Indian citizenship even though they are born there.

The twins, who are not Irish citizens either, are then welcomed home at Dublin Airport after the Irish authorities -- who do not regulate surrogacy in any way -- issue emergency travel documents.
Ultimately 'Her Body, Our Babies' will leave you with a deep sense of anger at the failure of the Irish authorities to regulate IVF and surrogacy.

Successive governments have turned a blind eye to the reality that hundreds of couples, gay and straight alike-- as well as single mothers -- are bringing home babies that are stateless and who do not have full legal relationships with those raising them. We have, once again, kicked the issue to touch and are leaving it up to the judiciary to deal with.

Next month the Supreme Court will sit as a full, Constitutional court, to hear a landmark appeal involving an Irish couple who also had twins via a surrogate, this time the genetic mother's sister.
It is inexcusable that our lawmakers have not dealt with the issue before now.
http://www.independent.ie/