A YEAR-END MESSAGE FROM A PATIENT: How a physician-patient feels about fertility treatments
By Promila Rao, MD, MHA, an internist and hospital executive. She can be contacted through The Reproductive Times.
Briefing: A large majority of the Center for Human Reproduction’s patients are not local to NYC but often travel long distances to receive treatment. One such patient is the author of this unsolicited article, which was unexpectedly received one day in the editorial office of the VOICE. What makes this communication, moreover, especially unique is the fact that the author—as will quickly become apparent—is a practicing internal medicine physician who, in addition, has considerable managerial experience as a senior administrative officer in a general hospital in her home state. We felt that her view of the infertility world was insightful and worth sharing.
I would like to give a shoutout to the CHR and Dr. Norbert Gleicher (the CHR’s Medical Director and Chief Scientist) and others who are similarly dedicated in their pursuit of science and truth and to delivering individualized, patient-focused care rather than relegating everything to an algorithmic approach based on dubious data.
ACCEPTANCE: A FUNDAMENTAL HUMAN NEED
Evolution has programmed us to say and do things that are widely accepted by society because acceptance is the most fundamental of human needs. Our very survival and wellbeing depend on being accepted. However, progress cannot be made by conforming to the status quo.
Discerning and brave voices that deviate from the mainstream narrative are necessary for bringing into focus the issues that require further scrutiny. For example: success rates for blastocyst vs. cleavage stage embryo transfer, fresh vs. frozen embryo transfer, the pitfalls of preimplantation genetic diagnosis for aneuploidy (PGT-A) testing for patients, the pitfalls of embryo grading based on blastomere symmetry, the pitfalls of “discarded per protocol,” and the recognition that egg and embryo quality may very well suffer if exposed to excessive hormonal stimulation—just to name a few.
THE FUTURE BELONGS TO THE BOLD AND THE INNOVATIVE
People who conform to status quo and focus on the bottom-line seldom make history. The future heroes of the fertility industry will be the ones who see a way to break away from the lure of a volume-based approach that targets the low-hanging fruit in a narrow age range and recognize that new advances are needed because it is no longer enough to replicate variations of what was done in 1978 with mixed results. The future of humanity may very well be at stake.
Has Reproductive Endocrinology stagnated like Physics, where endless debates on Einstein’s ‘Theory of Relativity’ and the ‘String Theory’ have been the norm since the 1970s with little further innovation? Is it not time for a quantum leap to break out of the time warp and meaningfully address of today’s issues?
Fortunately, we don’t live in a hyper-regulated society which rationed care. This allows us to leverage current research and apply it to provide better outcomes by exploring novel options and technologies.
HIPPOCRATIC OATH AND OUR RESPONSIBILITY
As physicians, we all took the Hippocratic oath, whose principal premise is “Primum non Nocera” (first, do no harm). Aside from the obvious implicit in that oath, is the recognition that we as physicians possess consequential knowledge and are tasked with guiding patients towards outcomes that are better than what would occur without our intervention.
SHIFTING ROLE OF MEDICINE IN SOCIETY
Today, physicians are called upon to solve problems that are not just simple “diseases” with well-understood etiologies such as polycystic ovary syndrome (PCOS). We are living through a time where multiple factors play a role. An increase in chronic illness and cancer in the US is a manifestation of what is wrong with our food and environment.
In addition, the very structure and dynamics of society have been upended. Due to decimation of the family structure and of traditional values, people are more disconnected than ever before. Masculinity itself has reached a crisis point as society has lost the art of imbuing men with a sense of pride, integrity, and purpose by providing male role models. This is the reason why reproductive endocrinologists are seeing a rising number of successful and healthy women who are childless not by choice but rather due to societal conditions. Hopefully, advances in science can bridge the gap for women, as we undertake the herculean task of improving society and resolving the crisis of masculinity.
INFERTILITY EPIDEMIC VS. SOCIETY IN CRISIS & HOW STRONG MOTHERS CAN SAVE THE FUTURE OF HUMANITY
Let us examine the current definition of infertility as it has evolved to become more inclusive to cover those who are not truly infertile. The traditional definition used to be ‘the inability of a couple to conceive after unprotected intercourse for 12 months under 35 or 6 months > 35 years.’ (Definition of infertility: a committee opinion (2023) | American Society for Reproductive Medicine | ASRM).
It would be interesting to see what percentage of the populations in fertility clinics is made up of successful, well put together, healthy women without fertility issues who are on this journey due to purely societal issues. Disempowerment of men and the decay of masculinity has led to suffering not just for men but also for the very women who crave normal, monogamous, and stable relationships with men.
While it may be the case that reproductive medicine helps those who suffer from infertility, it is not at all clear that, when it comes to normal non-infertile women in difficult social situations, it offers any outcomes approximating what nature provides if left uninterrupted. Additionally, there is potential harm due to invasive procedures and exogenous hormone exposure.
The prevailing messaging encourages healthy women to freeze their eggs to preserve fertility with scant data to help them decide where to seek care and no insight into the various pitfalls of oocyte vitrification. This allows for a false sense of security for women who are generously and lovingly trying to buy time to spare men from the pressures of the biological clock. However, these brave and generous women need to know that their live birth outcomes would be far better with nature, as the widespread protocols currently in use have significant limitations.
Should we leave any stone unturned to ensure that these strong, intelligent, independent, empathetic women become mothers and shape the future of humanity?
Furthermore, I would like to point out the obvious—the survival and non-extinction instinct is as strong in women as it is in men. Donor eggs do not offer survival and propagation of the gene pool for women.
THE FALLIBILITY OF EVIDENCE BASED MEDICINE, THE INCENTIVES FOR DATA NUDGING, THE DUBIOUS PLEASURE OF BLAME SHIFTING & THE LOST ART OF COMMON SENSE
I feel that my specialty (Internal Medicine) has become somewhat of a “manager of disease” with no cure in sight and a good bit of blame shifting towards the patient—often implying that if only the patient had a better genetic makeup, complied better with lifestyle measures, and with medicine, their disease could be better managed. Healthcare systems are rated on a Leapfrog scale (the Leapfrog Hospital Safety Grade is the only hospital rating focused exclusively on hospital safety. Its A, B, C, D or F letter grades are a quick way for consumers to choose the safest hospital to seek care) and have learned to manipulate data for financial gain.
It is incredibly easy to go from a Leapfrog score of C to an A. For example, in order to show lower mortality rates, inpatient hospice admissions are encouraged as they don’t count towards mortality. Instead of addressing root causes of patient safety incidents (PSIs), nurse managers are incentivized to ask doctors to not order C. difficile or urine culture with indwelling foley catheters, etc. End result: fantastic scores with no net improvement in the quality of care rendered!
I see a parallel in the Reproductive Endocrinology field, wherein several clinics amass vast numbers of patients in the desirable age demographic. This is followed by slicing and dicing data, eliminating outliers etc., to show amazing results. These results are then proudly advertised to attract even more patients and compete with other conglomerate clinics. The resulting high volumes are managed using protocol driven, assembly-line approaches with no focus on excellence of care or the individual patient.
I have experienced this myself when I vitrified 15 oocytes at age 41 in July 2014 with a South Carolina clinic rated among the top 10 in the US based on CDC live birth rate data as no vitrification data was available at that time. This was an age at which multiple women from both sides of my family conceived and gave birth to healthy children naturally. I felt confident in my choice as this clinic had a Donor Egg Bank Certification and several published studies demonstrated 95% thaw survival. Aside from that, my colleagues experiencing fertility struggles had success with this clinic. My estradiol peaked at 8898 pg/ml causing me to be concerned about ovarian hyperstimulation (OHSS) and it kept me from considering additional retrievals. I was told that my ovaries were the size of grapefruits but in-spite of my requests, no immature oocytes were either matured or vitrified and my suggestions were treated with indulgent humor instead of being taken seriously.
Following vitrification, I nevertheless felt I had bought time and felt fortunate that I had previously unavailable options for women that could ensure a 95% thaw survival rate of oocytes and, thereby, ensure the preservation of my fertility. Upon thawing my eggs in 2021 – three to four at a time - at a prominent clinic in New Jersey, the thaw survival was only a dismal 30% instead of the promised 95%.
In addition, embryologists of questionable competence and qualifications blindly discarded one of my blast-stage embryo “per protocol” with no input from my reproductive endocrinologist and, of course, I was kept in the dark and only found out retrospectively. I had not been given the option of culturing my embryos only to cleavage stage, but opted out of chromosomal testing of my embryos (PGT-A) testing based on my understanding that many embryos could self-correct their aneuploidies.
Now at age 50-51, I had to start all over again making embryos. I have made 7 cleavage stage embryos (most Grade B) which in itself is a miracle and speaks to the fact that my confidence in my family history was not unfounded. However, my confidence in my own profession and science has taken a huge hit as my achievable dreams suddenly feel out of reach. In addition, I have had to subject myself to additional exogenous hormones and invasive procedures due to the limitations of science. If someone with my level of fertility and knowledge can experience this, what is the hope for other women?
Our intuition/common sense is the result of millions of years of evolution and has ensured our survival and propagation. Prospective double blinded cohort studies are not needed to validate what we instinctively know to be right. We intuitively know that oocytes and embryos will do better if we reduce freezing/thawing stress, avoid inhospitable culture media, plastic culture dishes, etc. This is the only way to improve upon natural outcomes of the general population. Otherwise, assisted reproductive technology (ART) will always lag behind nature. Hopefully, we can build on existing research from people like Professor Mitinori Saitou, MD, PhD, at Kyoto University in Japan, Professor Shoukhrat Mitalipov, PhD, at OHSU in Oregon, and others to offer hope for the future of humanity.
SUMMARY & CLOSING REMARKS
We are all driven by a need for acceptance and belonging to a group; however, let’s not forget that we have instincts, a free will and a conscience that can guide us and has never led our species astray.
The future belongs to the bold, the innovative and upright. The pursuit of truth through science necessitates that we eliminate subversion and manipulation for personal gain. Data manipulation does not equal advances in fertility outcomes.
Let’s remember and re-avow to the Hippocratic oath: ‘Primum non Nocera.’ It should be possible to provide outcomes better than nature even for non-infertile women who are childless due to societal issues.
Women who are childless due to societal issues must be treated as a distinct population. These women need to know the limitations of science and current protocols such that, if they subject themselves to IVF, their live birth outcomes would be no better than those reflected by ART data for infertile women. They might be better off if they let nature take its course and just procreate as God intended.
Let us recognize the limitations of Evidence Based Medicine (EBM). Let us keep in mind that EBM does not mean we have to ignore common sense and our instincts or move away from individualized approach to patient care.
Let’s not forget that all of us, including—of course—our patients, are created equal in the eyes of God. Patients should be allowed full transparency, including time-lapse pictures of embryos. Decision-making regarding discarding an embryo or egg must include the patient and physician.
Future innovation must aim at minimizing invasive procedures and hormonal stimulation so that women, especially those who are in this situation due to societal issues, don’t have to sacrifice their health for a chance at having a baby.
This is a call to all my reproductive endocrinology colleagues to become the bastions of hope, the defenders of truth even when it is unpopular, and the protectors of women and thereby the future generations. Educated and compassionate women raise stable and productive children who can change the course of humanity for the better.
Let it not be said that reproductive endocrinologists stood by and allowed the world to be overrun by other species such as mice, monkeys, cloned dogs, sheep, beauty camels, and even the wooly mammoths, while many wonderful women were admonished based on age, failed by medicine when they tried to preserve fertility, judged for the shortcomings of men and society, and, ultimately, led to extinction as no one could figure out how to do things better. Please help save this valuable endangered species that is at the brink of extinction.
Finally, let’s consider the future with AI. If AI is fed erroneous/manipulated data through large language models, what would the future of our species be? AI has the potential to be the only God-like entity without morals and emotions. To what extent can we appeal to AI? While God is capable of love and compassion and forgave humanity without us bearing the burden of proof, the same cannot be said of AI or its creators.
Our hope lies in future generations possessing bravery, intelligence, and integrity passed on to them by mothers who possess these qualities. The pursuit of truth that is shared by both religion and science needs to be the primary quest for humanity. This requires freedom of thought and speech and individual autonomy. In conclusion, whosoever ensures that good mothers propagate and are not led to extinction will save the world!