As Head of Global Development and Medical for Merck Germany, my responsibility is to advance our pipeline, focusing on efficacy, safety, and differentiation, so that we can deliver meaningful value to patients with serious medical needs. We have more than 2,300 people working globally in R&D, with four strategically located hubs on three continents: Boston (United States), Darmstadt (Germany), Beijing (China) and Tokyo (Japan). And we invest more than 1.2 billion Euros every year into R&D, to advance innovation throughout our discovery efforts and our pipeline. We at Merck focus our efforts on several therapeutic areas, including oncology, multiple sclerosis and an area in which we have an unparalleled legacy, and that is infertility, with expertise and experience dating back to the 70s. Today, our efforts at Merck Serono to expand our understanding of infertility have advanced significantly, with our products sold in more than 105 countries, contributing to 1.6 million IVF cycles over the lifetime of our portfolio, bringing hope to thousands of families who want a child.
The broader landscape of infertility has evolved in tandem…driven by the empowerment of women to choose their own reproductive path, by the full spectrum of opportunities available to women to choose professional success first and children later, and by new options in technology and therapeutic approaches that offer more choices and solutions to a woman who faces infertility. I would like to spend some time today sharing a perspective on fertility and its counterpart and how these have evolved over the last three decades, and offer insight on the implications for the changes that are occurring globally – for society, for women, and for future generations.
The foundation of my talk will focus on choice, and the paradox it has created in the context of fertility. Certainly, the body is not the only consideration when it comes to childbirth. It is, of course, also a conscious decision to choose—many would argue the most significant thought-process a woman undertakes during her lifetime – because from the minute your child is born, your life is forever on a different path. The factor of choice and a woman’s ability to define her own reproductive destiny has changed over the years, and is a driving force in the shifting fertility landscape.
Today, as we stand in 2013, having a child has evolved from something given – it was expected 60 years ago that all women want and have children and raise a family – to a decision, and this is clearly reflected in the data. The key trends have reshaped the fertility ecosystem, telling a compelling story as to why choice has created such a paradox.
In 1950, during an era of set expectations around women and children, the average woman had five children during her lifetime. Today, that number has dropped to an average of jUSt over two, and will continue to drop to under two by the time we reach 2050 and beyond, if the forecast holds true. Here, we get into the complexity of the evolution of fertility, physiology and choice, and its impact on society. As a result of the dramatic shift in the number of children being born, many parts of the world are facing a flat population line or a decline, including the US, Brazil, Canada, Australia, parts of Europe, and parts of Asia. Germany, where the headquarters of Merck are located, is an excellent example of the issue at hand: As recently reported in “The Economist”, with the world’s second oldest population (after Japan) and one of the lowest birth rates in Europe, the country is facing a demographic bust. There is a clear reason for this drop in volume, and again we come to choice – women are choosing to wait until later in life to conceive.
In many developed countries across the world, the average age at which a woman has her first child has increased by approximately four years over the last four decades, shifting from her early twenties to mid to late twenties. In the US, for example, the average age of first birth went from 21 in 1970 to 25 in 2006, while Switzerland went from 25 to 29 across the same timeline. This creates two issues: First, her reproductive window of opportunity is shorter – she has less time to have children. Also, as women age, their oocyte quality and quantity drops. While both are considered optimal in a woman’s 20s, they start to decline quickly in her 30s with a marked drop after 35.
To give you a sense of the numbers, a woman is born with about one million eggs in her ovaries. By the time she has her first period the quantity falls to less than 400,000. The remaining eggs lie dormant and are activated by hormones during the monthly cycle. Over time, as a woman ages, the number of eggs that are available to be released, decreases, and the remaining eggs accumulate defects, making it harder to have a child and increasing the risk of a birth defect.
While women are having fewer children, later in life, they generally still make the conscious decision to start a family. What influences the decision child for a woman, regardless of her age? Findings from the international fertility decision-making study “Starting Families” indicate that the primary drivers for a woman in deciding to have a child are economic preconditions: Is her job secure? Has she reached a desirable level of success professionally? And how will having a baby affect her career? And secondarily, there is a focus on the status of her relationship with her partner: Are they both ready? Is the relationship stable? Will having a child bring personal fulfillment?
Cultural norms play a role as well in assessing whether or not to have a child. In India, for example, the social value of children is a decisive factor in the decision to conceive, whereas personal desire is less important. In Denmark, on the other hand, relational and personal readiness is ranked highly as a decisional factor, while social value is not.
So while many women are waiting until later in life to conceive, others are choosing not to have a child at all…and this is a choice that is most striking across Generation X. In this generation, which concerns people born between the years 1965 and 1979, according to research done by the Center for Work Life Policy, 43% of women choose not to have children. Among US men and women ages 25 to 29, roughly a third say they would only be bothered just a little or not at all, if they wound up not having children. Nearly half of women aged 30 to 44 felt similarly. In the UK, a fifth of all women born in 1975 or later will remain childless, and a quarter of women with university degrees will not have had children by their 40th birthday. In the US, the figure is even higher: 24 percent of college-educated women do not have a child at age 40. Looking even further, the research revealed that 26 percent of women without children ages 40 and over are, in fact, married or have a partner. While the numbers speak for themselves, they are founded on clear, rationale thinking, with qualitative findings indicating several reasons that this choice is becoming more and more common: financial constraints, the aversion to “extreme parenting” that is an expected part of raising a child today, having full-time demanding jobs, and because “gen Xers” simply don’t want to give up their freedom.
As the economy fluctuates globally, downturns also play a significant role in the decision to remain childless. Looking at the US, the fertility rate there has fallen sharply, since the nation went into recession in 2007, hitting the lowest rate ever reported in 2011 and staying there in 2012. According to the CDC, there were 63.2 births per 1,000 women ages 15 to 44 in 2012, down from 69.3 births per 1,000 women in that age range in 2007.
The decision to not have a child or the decision to wait until later in life to conceive is increasingly becoming legitimate and acceptable across cultures. However, the latter is not without physiological implications. Waiting to conceive creates a risk. While waiting until later in life allows a woman to build her career and to focus on professional success, it’s a paradox : You flourish in one area but create the potential for risk in another. Think of it as “reproductive roulette”…you might get lucky, but you might also have serious trouble.
Once the choice is made, a new set of questions arise: Will the body cooperate? Will a woman still be able to conceive? Will she have the opportunity to have as many children as she wants? Infertility, which is defined as a delay or difficulty to conceive a child after one year of unprotected intercourse for women younger than 35, or after six months for women older than 35, is an equally complex issue as the path to deciding to have a child.
Let me provide some basic percentages about fertility, health, and conception. On average, for a woman with no fertility issues, who is trying to conceive, the chance of success per month lies at about 20%. After a year, in all likelihood she’ll be pregnant – with the odds above 90%. For a woman dealing with infertility, which presents itself in many ways, her chances of conceiving within a year are about 14 to 20% if untreated. With treatment using medication or assisted reproductive technologies (ART), her chances are greater than 80% over the course of one year of treatment.
The number of women facing infertility has increased over the last decade, as choice has delayed childbirth until later in life. To underscore this point, looking at a select sample of nine countries across Europe, eight have seen an increase in the number of IVF cycles over the time period from 1998 to 2012 alone, with Denmark experiencing the most dramatic increase from 1,600 cycles of IVF per million people, to 2,450 cycles, which represents about a 53% uptick. IVF, if you’re unfamiliar, is in vitro fertilization, a major treatment for infertility when other methods of assisted reproductive technology have failed.
Most women who seek medical support in trying to conceive are between the ages of 35 and 40. A woman’s odds of success in terms of actually having a baby are directly related to her age – at age 30 the chances conceiving through ART are about 50%. At age 40, that percentage drops to 15, and at age 45 to 3%.
There are two problems that obfuscate the choice to have a child for a woman who waits until later in life to try to conceive: on the one hand her body clearly might not be on board, as the percentages indicate, and on the other hand most women simply don’t understand the correlation between age and fertility. Let me take a moment to explain: The ovarian age and chronological age are not in agreement. A 40-year-old woman is young, but in fact her ovaries are old. Many women think that because they continue to have a menstrual cycle, that they also remain fertile, which is absolutely incorrect. Age is the most impactful variable in the paradigm of infertility. And actually, most women are unaware of the resources available to them to help treat potential physical problems.
Out of 100 women who are struggling to conceive, 56 will not seek medical support, and of the 44 that do, 19 will not see through the full process to maximize their potential of having a child. Cost, education around infertility treatments, and social stigmas all serve as barriers to overcome this issue, but arguably, understanding and being aware of infertility is inherent in its legitimacy as a valid medical condition among women. The fact that more than half of women don’t turn to proven methods of increasing their odds for conception is troubling – we still clearly have work to do. And meanwhile, science needs to advance as well, because, to put it simply, the more science we have, the more we have to offer women in supporting their determination to conceive.
IVF was first successful over 30 years ago, and it is still today the foundation of ART. Looking back on our progress, revolutionary innovation was the application of hormones, specifically, human menopausal gonadotropins, to treat infertility. At the time this was a disruptive idea considering these were isolated from the urine of post-menopausic women, in fact from Italian nuns. Evolutionary innovation was exemplified by the improvement of urinary products with recombinant ones which are more pure, have a higher biopotency, and are a more reliable biotechnological source of production. Today, to be innovative, we need to set the status quo, and be inspirational. We have to offer new approaches in infertility that add value for a woman who has chosen to have a child, as well as benefits showing their significant advantages over the cost. A core element of treating infertility is remembering the human component of the condition, and connecting this to innovative, breakthrough ideas that will help us see new possibilities. As I mentioned earlier, a woman undergoing IVF has a 80% chance of successfully having a baby over the course of several attempts, but in an average single IVF cycle, of 100 women, only 36 have an embryo implantation, and of those about 30% have a child. And this statistic is felt worldwide, with the US having the best rates, followed by Europe with a 15% success rate, and Japan around 7%. This lack of efficacy is related to embryo implantation failures in 80 to 90 percent of the cases and the other 10 to 20 percent of the time to uterus receptivity. One of the biggest problems we have in IVF is the lack of objective technologies…technologies that can identify the right embryos to transfer (those that have the highest implantation potential) as well as the receptivity status of a woman’s uterus in terms of its ability to implant the embryo successfully.
So, today, identifying new opportunities to advance science and technology of infertility should be a priority in healthcare. While we’ve come a long way, there is still a long road ahead as women balance the paradox of careers and families, as more women choose to have a child later in life, and as more women become aware of and understand infertility and the treatments available today and in the future.
While breakthrough innovation is crucial to leveling the fertility playing field, so is the support that is available to women across the spectrum of reproductive choice—younger women, women who face infertility as a physiological challenge, and women who delay conception until later in life. Globally, we need to be very aware of this diversity, as we assess fertility trends and the decision making process people undergo when they consider having a child. What we have today in terms of support, programs are at best, modest. While financial incentives offered in some countries help, they’re offset by the tremendous cost of raising a child, not to mention the cost of ART and IVF for the uninsured or underinsured—a huge issue in and of itself when it comes to infertility. While employers offer flex-time and parental leave, do these impact a woman’s ability to be successful professionally? More and more, we are seeing shifting societal norms that make the decision to not have children an easy one.
As we look at the picture again, we can now clearly see the paradox. The value of choice is immeasurable, but with each decision comes a consequence. To wait to have a child, to have a career first, to have fewer children…all of these have implications on oneself, on society, and on the whole world.
As we look at the future of fertility, we know it will evolve and the options available to women will diversify. And this is the imperative: to provide science, therapies, technologies, and programs that will arm women with the tools required to continue to have a choice. To change the paradox into new possibilities.