Worcester Medicine January/February 2022 by wdms

medicine worcester Volume 91 • Number 1

Published by Worcester District Medical Society January / February 2022

INFERTILITY: AN OFTEN SILENT STRUGGLE

Infertility/Decreased Fertility: Significant Positive Changes in the Last 30-40 Years

An Infertility Story: One Woman’s Experience Building Families: Educating our Next Generation of Physicians

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Contents

JANUARY / FEBRUARY 2022

Editorial 4

on the cover Day five high grade human blastocyst

Delaying Childbearing During Medical Training 14

Heidi Leftwich, DO

Gianna Wilkie, MD

President’s Message 5 Spiro Spanakis, DO

From the Archives

Infertility

B. Dale Magee, MD, WDMS Curator

Infertility/Decreased Fertility: Significant Positive Changes in the Last 30-40 Years 5

Legal Consult

The Birth and History of IVF 15

Julia V. Johnson, MD

States of Emergency 16 Peter Martin, Esq.

An Infertility Story: One Woman’s Experience 6 Marianne E. Felice, MD

Building Families: Educating our Next Generation of Physicians 8 Christine Van Horn, MD Jennifer Yates, MD Haley Schachter

As I See It

Universal Newborn Home Visits 18 Sheilah H. Dooley, RN, BSN, MS

Society Snippets

Worcester District Medical Society 2021 Fall District Meeting & Awards Ceremony & WDMS 2021 Scholarship Award Recipients 19

Planned Oocyte Cryopreservation 10 Armando Arroyo, MD Yanguang Wu, PhD

In Memorium

Medications Used for In Vitro Fertilization 12

Dominic J. Nompleggi, MD, PhD 22

Anna K. Morin, PharmD

John Zawacki, MD

published by

wdms editorial board

produced by

Worcester District Medical Society

Heidi Leftwich, DO, Guest Editor Lisa Beittel, MBA Anthony L. Esposito, MD Rebecca Kowaloff, DO Anna Morin, PharmD Nancy Morris, PhD, ANP Thoru Pederson, PhD Joel Popkin, MD Alwyn Rapose, MD Parul Sarwal, MD Robert Sorrenti, MD Ram Upadhyay, MD Peter Zacharia, MD Alex Newbury, MD Resident Representative Pawina Subedi, MD Resident Representative

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Worcester Medicine does not hold itself responsible for statements made by any contributor. Statements or opinions expressed in Worcester Medicine reflect the views of the author(s) and not the official policy of the Worcester District Medical Society unless so stated. Although all advertising material is expected to conform to ethical standards, acceptance does not imply endorsement by Worcester Medicine unless stated. Material printed in Worcester Medicine is covered by copyright. No copyright is claimed to any work of the U.S. government. No part of this publication may be reproduced or transmitted in any form without written permission. For information on subscriptions, permissions, reprints and other services contact the Worcester District Medical Society.

WORCESTER MEDICINE

Editorial Heidi K. Leftwich, DO

nfertility is more common than people acknowledge,

with some data reporting as high as one in eight women struggling with infertility in the United States. As important as it is to acknowledge the medical causes of infertility and the stress on the health care system, it is just as important , if not more so, to acknowledge the physical and emotional toll on patients and couples struggling with infertility. The title of this issue reflects the struggle patients feel when they, too often, sit in silence. We are fortunate to have authors from many aspects of health care sharing their stories and expertise in this field, with some sharing deeply personal stories. I feel very fortunate to be the editor of such a powerful volume of Worcester Medicine. My own intimate encounter with infertility began in residency. I married relatively young, in my first year of medical school, and while children were in the plan for us as a couple, we were happy to wait until things were “more stable,” whatever that meant. This was a common theme in residency, as our work hours were long and unpredictable, and it seemed there would always be a better time to have kids. However, in residency, a few of my colleagues had children and I watched intently as they navigated these long, unpredictable hours and parenthood. I was longing for the same. My husband and I had decided there would never be a “good time” and decided pregnancy during residency would work for us, especially as I was planning a three-year fellowship. As an obstetrics and gynecology resident, I had the distinct pleasure and privilege of delivering many babies, which I will admit became harder and harder as the reality of infertility set in. I longed for the ability to have that moment as well. While sitting with colleagues in break rooms and on the labor floor, many would ask when I was going to have children and when I said we were trying but I had not yet conceived, many reassured me my time would come when I was “less stressed” and “working less.” For a while, I believed them. After years of not conceiving, I decided to reach out to my colleagues in infertility for a work-up. I was conflicted when I heard the news that we would need in vitro fertilization, or IVF, to conceive. However, I was arguably a little relieved it was not my career choice that had landed us childless. Fast-forward to the time of multiple appointments and blood draws during an 80-hour work week in your own department, all while trying to be secretive as I did not want to share this journey with all of my colleagues. What I know now and did not know then was how vastly important it was to share this journey. With someone. With anyone. I felt so alone. The title of this issue expresses my own silence as well as the many others who experience this journey – openly or in silence. My first IVF cycle ended in a miscarriage at seven weeks, which presented itself with a significant bleed while I was operating. This was emotionally difficult as I was certain I was losing the pregnancy and had an additional component of having to tell my male attending and find coverage

for the case while I lost the pregnancy otherwise in silence. It was my 30th birthday and not the way I had planned to celebrate. I had friends over that night and aside from my husband, told no one. My next two cycles of IVF were much happier times. They each were successful and I now have two daughters, Harper (9) and Hailey (6) , due to the wonderful technology, hard work, robust research and dedication from those who work in the field of reproductive endocrinology, or REI, and infertility. I could not be more grateful every day for this opportunity. As a maternal-fetal medicine specialist, caring for patients with high-risk pregnancies, I feel I can share a more personal connection with those struggling with infertility and those who have made the journey through IVF. I try to ensure others do not endure this in the silence I once did. I am fortunate to have an article from the head of our own IVF center at UMASS to provide information on infertility care in Central Massachusetts. I was thrilled to hear from the former chair of the Department of Obstetrics and Gynecology, an REI physician, for this issue, as she was instrumental in the creation of this IVF center. This issue is also filled with stories regarding the struggle women in medicine face delaying starting a family, and often choosing a career that would allow them flexibility to start a family. As you read these articles, some quite intimate and personal, it is my hope you gain a better understanding to the condition of infertility and how it may impact your patients, family and friends. Thank you for the opportunity to serve as the editor of this very important volume. + Heidi K. Leftwich, DO Assistant Professor, Obstetrics and Gynecology Associate Fellowship Director Division of Maternal-Fetal Medicine University of Massachusetts/UMMC

“

What I know now and did not know then was how vastly important it was to share this journey.

JANUARY / FEBRUARY 2022

”

WORCESTER MEDICINE

President’s Message

Infertility

Infertility/Decreased Fertility: Significant Positive Changes in the Last 30-40 Years

Spiro Spanakis, DO

Julia V. Johnson, MD

app y N ew Y ear to all ! O vershadowed by the pandemic, and unsettling current events in 2021, I hope 2022 brings health and harmony to you and your families. Despite the pandemic, the Society continues to be active on many fronts. At our recent business meeting, more than 20 scholarships were awarded to deserving medical students as they face the rising costs of medical education. I encourage you to contribute to the Worcester District Medical Society scholarship fund on our website. Recently, the district’s medical student committee, chaired by student doctor Bennet Vogt, sponsored a successful virtual anti-racism and health equity forum. The event enlightened us all and provided a wonderful platform for discussion. Special thanks to Dr. Anne Larkin for her support of this committee and the event. I also want to, again, congratulate Dr. Kavita Babu, M.D., the recipient of our Dr. A. Jane Fitzpatrick Community Service award and Dr. Thomas Halpin, the recipient of our WDMS Career Achievement award. As I prepare this message, the district’s delegation to the Massachusetts Medical Society is preparing for its virtual interim meeting. Becoming a member of our delegation is an excellent way to meet new colleagues, learn about issues facing medicine and better understand the legislative process and important ways we, as individual physicians, can make a difference. We always have unfilled seats on our delegation so we please contact the WDMS office via email at mwright@wdms.org, if you are interested in learning more about this opportunity. I am pleased to announce Dr. Kimiyoshi Kobayashi, UMASS Memorial Health’s chief quality officer, will be the society’s 226th orator. Please watch for announcements about this and other upcoming events. +

L o u i s e B r o w n wa s b o r n i n 1978, the first child conceived through IVF, there has been marked improvement in the diagnosis and treatment of infertility for men and women. Although insurance companies in many states do not recognize this common disease, it effects at least 12% of women and 15% of married men in the U.S. Fortunately, the awareness of this disease, and the effectiveness of treatment, has increased. In 2017, the American Medical Association joined the World Health Organization in recognizing decreased fertility/infertility as a common disease of reproductive aged women and men. Now, 15 states offer some coverage for this disease with Massachusetts being one of the first to mandate private insurance coverage for infertility. The causes of infertility are complex, yet the evaluation has been simplified significantly during my years as a Reproductive Endocrinologist/Infertility (REI) Subspecialist. The causes of infertility include low sperm count or motility or ‘male factor’ (35%). ‘Female factor’ (45%) includes the most common cause, tubal or uterine disease (30%) with the next most common as ovulatory dysfunction (15%). The remaining causes are unexplained (20%). In the early years, testing was complex, involving cervical mucus testing, endometrial biopsy, specialized sperm testing and repeat hormonal testing. Currently, a doctor obtains a simple set of tests to confirm multiple factors, including: ovulation (ovulation predictor kit or progesterone level in the luteal phase), assurance of a normal uterus and fallopian tubes (ultrasound or hysterosalpingogram), hormonal tests to evaluate ovulatory disorders or rule out premature ovarian dysfunction, and a semen analysis. All testing can be done in a month at modest cost by an experienced REI at UMass Memorial. And treatment is now also straight forward. In the past, complex surgery was done to fix scarred fallopian tubes with poor success and ovulation induction was overused with the risk of multiple gestation. There was no treatment for male infertility except trying intrauterine inseminations (with limited success) or donor sperm. Now, the only reason for surgery is severe pain (endometriosis), to clip fallopian tubes (and increase pregnancy rates) or remove lesions from the uterine cavity (polyps and fibroids). Only oligoovulatory and unexplained infertility patients use ovulation medications and then only in limited amounts. For women with ovulation dysfunction (such as PCOS), 50% become pregnant within six months; if very mild, male factor is added and an intrauterine insemination can be considered. For other causes, if surgery is not indicated first, then IVF may be the best treatment with pregnancy rates per cycle of 40-50% for women under age 35. The success with IVF treatment has increased from 8-10% per cycle when I started in 1988 to 40-plus percent per cycle currently. IVF treatment is highly successful for male factor, tubal factor, uterine factor, ovulatory dysfunction and unexince

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

Infertility

Infertility/Decreased Fertility Continued

plained infertility. The standard of care for infertility treatment is clearly established. The only remaining issue is decreased fertility based on advanced maternal age, which continues to be a challenge. Fertility rates naturally drop for women as they age with a decrease in pregnancy rates and increase in miscarriage rates beginning in the mid-30s. If couples ‘save’ their money for infertility coverage, they may miss a critical window for optimal treatment. The sad story is that the evaluation is brief and simple, and the treatment is highly successful for younger women/couples The issue for those with infertility is routine insurance coverage. The typical argument made against an insurance mandate for evaluation and treatment of decreased fertility/infertility is the cost. Indeed, in countries such as Denmark and Belgium, which cover treatment, the IVF rate is high – 12,500 IVF cases per 1 million women aged 15-45. However, studies have demonstrated the relative cost of infertility coverage is relatively modest. New York state estimated insurance premiums went up by 0.5% when infertility treatment, including IVF, was included in private insurance. For individuals without coverage, the cost can be problematic, with the average cost for an IVF cycle costing $12,000 (with more than one-third of the cost being medications). It is a positive factor that Massachusetts was one of the first states to mandate infertility coverage, recognizing this disease as requiring private insurance coverage. Although, the insurance companies put up many barriers (such as excessive testing) to delay treatment, the services are available throughout our state. Although infertility evaluation and basic treatment has been available at the University of Massachusetts Medical Center for many years, the institution now has the only IVF program in Central Massachusetts. Even in Massachusetts, however, there are limitations to covering the disease of decreased fertility/infertility. There remains inequity in covering the costs of this standard evaluation and treatment. Government insurance has no coverage for public or federal employees, although there is limited coverage for veterans whose injuries resulted in infertility. State insurance programs, such as Medicaid, may cover infertility testing but does not cover treatment. This leads to a significant disparity of treatment for those who are economically disadvantaged, many of whom may come from Black, Chinese and Hispanic communities. Often, these individuals have several jobs yet elect not to obtain private insurance due to the cost or lack of availability by the employers. I encountered this frequently at UMass and encouraged patients to obtain private insurance leading to coverage of infertility treatment as a modest cost. This allows the underserved in our community the right to have their disease treated and the family they desire. In summary, infertility is clearly a common disease of reproductive aged men and women and the current evaluation is straight forward and the treatment is effective. Encourage your patients to see an REI specialist, including those at UMASS in our IVF program, to discuss their circumstances, take a brief evaluation and consider the best treatment for their disease. We are most fortunate to live in a state that respects the reproductive rights of women and men. + Julia V. Johnson, MD, is a Professor Emerita and Former Chair of OB-GYN at the UMass Chan Medical School and UMass Memorial Medical Center. Following retirement in 2020, she is now at the University of Vermont College of Medicine/UVM Health Care as a Professor and member of the Faculty Training Residents and Fellows in Reproductive Endocrinology and Infertility.

JANUARY / FEBRUARY 2022

An Infertility Story: One Woman’s Experience Marianne E. Felice, MD

ohn and i married late; we were both

35. In our 20s, when most people marry, we were starting our careers. John was career Navy and I was in medical school. When I was a pediatric intern in Harrisburg, Penn., he was assigned to Harrisburg for recruiting duty. He tried to recruit me into the Navy. I declined, but agreed to go on a date. One date led to another and, after seven years of dating, we were married in San Diego, Calif.. There, I accepted a position at University of California San Diego as chief of adolescent medicine and he was assigned duty at the naval base. We presumed we would have children, never thinking it would be difficult. I began looking for au pairs and day care options. John balked and stated he would retire from the Navy and become a stay-at-home dad. I was aghast. “Why?” he asked. I said, “Because this baby will be smoking cigars and playing poker and cussing like a sailor before it reaches its third birthday!” He laughed. “Yes, and that is if it’s a girl. Imagine what I will do if it is a boy!” We tried with no success. Two years later, we had an appointment with a fertility expert. We did everything he said to do. tracked my temperature daily with that special thermometer to hone in on ovulation. I did not think John was paying attention to my daily ritual until one evening, when he was in the shower, I turned down the bed and a note was pinned to my pillow: “Signal, when ready!” John booked us on cruises so I would be away from work and relaxed. The cruises were great, but a pregnancy did not happen. We were both evaluated for infertility with no causes found. One procedure was memorable. We were scheduled for an in vivo fertilization at the time of ovulation. At the doctor’s

WORCESTER MEDICINE

Infertility

An Infertility Story Continued

office, John was sent to a bathroom and I was placed on an exam table with my feet in stirrups. John’s semen was introduced into my vagina with something that looked like a turkey baster and my exam table was tilted so that my head was down and my bottom was up. John came into the room and we were instructed to think romantic thoughts. The nurse left the room. John and I did not speak for at least one full minute. Finally, he asked me what I was thinking. “I am thinking that if your sperm are not bright enough to find my eggs unless I am turned upside down, I am not sure I want them anywhere near my eggs!” “Wow,” he replied. “Now that is REALLY romantic! Relax, honey. I am pretty sure my sperm will find your precious eggs!” Then he held my hand and I cried. But nothing seemed to work. As time went on, and I was approaching 40, I was acutely aware of the increasing risk of having a baby with chromosomal anomalies. If that happened, John was adamant we would have an abortion. I am Catholic. I was equally adamant I would not. In the long run, it was a moot point. Then, we considered adoption. Since John was a Protestant, the Catholic agency we contacted would not accept us as adoptive parents, even though John had signed a document when we were married in a Catholic ceremony agreeing if we had children we would raise them in the Catholic faith. We contacted another agency. They met with us but determined that because John was in the Navy, I would often be raising the baby alone while he was at sea. They preferred an intact family and not a single mother. John said he would retire from the Navy if we had a child, but that was dismissed. I was horrified to think my husband, who had served in the Vietnam War, was now being penalized as a military man who wanted to adopt. (President Gerald Ford, who was adopted himself, had that rule overturned later.) So, we pursued private adoption. This was after the passage of Roe v. Wade, so there may have been fewer babies to adopt. I found the name of a lawyer who specialized in private, open adoptions. She found an out-of-state pregnant teenager who was coming to San Diego to live with a relative until she delivered. We agreed to pay for her prenatal care plus additional adoption fees. We learned she was having a baby boy. We were asked to write a letter stating why we wanted to adopt. Another family also wanted to adopt and were writing a letter as well. She chose our letter and we were scheduled to meet with her. That is when we learned her pregnancy was the result of date rape. John was concerned we might be raising a future rapist. His literature search at the public library did not support such a fear, but he was dubious. We then learned she wondered if we could adopt her as well as the baby. Or, at minimum, would we let her live with us. That unusual request worried me. What if she did not like the way we were raising her baby? Would she take him away? The adoption fell apart. We later learned the other family did adopt this little boy. The young mother went back to the Midwest and did not ask to live with the other family. John and I were both shaken by the experience and decided to hold off on future adoption efforts for a little while. I remember that day well because, after we left the lawyer’s office, John went to his office at the

Navy base and I went to my afternoon clinic. As fate would have it, that day was the day that, together, the pediatrics and OB-GYN departments held the weekly teen pregnancy clinic. I put on my lab coat and greeted the 15-year-old patient in room No. 1 who was 24 weeks pregnant. The irony was not lost on me. Although adoption did not work out for us, I am a strong believer in adoption. It is usually good for the child, but it is also good for the generous adoptive parents who are willing to open their hearts and their homes to children who need them. John and I did not end up adopting a child, but we have had the good fortune of being involved in the lives of several children. We helped my elderly aunt raise her granddaughter when the child’s mother left her and her father passed away. She lived with us briefly until her mother returned. I became very close to one of my nieces when she was a teenager. We took her to Paris and London and on a cruise to Hawaii. She is a mother herself now and lives in another state. We are still close and talk by phone nearly every week. I also have two godsons (brothers) whom I love. Their mother, my good friend, passed away a few years ago. I officiated at the wedding of one godson and served as mother of the groom for the other. By coincidence, one godson’s bride was a woman I had actually held in my arms when she was a baby. I did not realize this fact until I was at their wedding and her grandmother recognized me and told me the story. I do not know why I was not given the gift of being a biological mother, but if I am lucky enough to get to the pearly gates when I die, it is one of the first questions I will ask the good lord. In the meantime, I relish my good fortune to have so many young people in my life. They are not my children, but I love them as if they were. + Marianne Felice, M.D. is Chair Emerita of Pediatrics and Professor of Pediatrics and PB-GYN Emerita at the University of Massachusetts Medical School. Email: mariannefelice@townisp.com I am grateful to Dr. Tiffany Moore-Simas, Chair of OB-GYN, for her excellent editorial suggestions.

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

Infertility

Building Families: Educating our Next Generation of Physicians Christine Van Horn, MD Jennifer Yates, MD Haley Schachter

enerations of physicians have walked a

tightrope — balancing dedication to patient care, career aspirations, personal goals and interests, and, in many cases, starting and raising a family. We are fortunate to see many changes over the past decade, with more attention paid to quality of life, burnout, work-life balance, and overall physician and provider wellness. We, as physicians, regardless of our specialty, have undoubtably offered our time, energy and expertise at some point in our careers to support our patients as they become pregnant or adopt, raise children, and thrive as parents. Our colleagues in the Obstetrics and Pediatrics department come to mind as physicians committed and dedicated to this cause. Surgeons and medical specialists take into consideration how the diagnostic tests and treatments we offer impact patients’ fertility and ability to raise a family. For example, our Radiology colleagues are dedicated to limiting the risks of radiation to our patients of childbearing age. But, do we excel at protecting and educating ourselves and our colleagues, our trainees and their families? Historically, this aspect of our lives as physicians has not been an area of research or advocacy. A recent New York Times article highlighted what many physicians already knew from small studies within our own specialties: our chosen career path and, for most of us, our passion, can be at the expense of our own fertility and pregnancies(1). In this article, Jacqueline Mroz describes the challenges female physicians face, including delaying childbearing until after training, infertility and the poor health outcomes that have been described in pregnant physicians. This should be a burning platform, an epidemic of infertility and higher risk pregnancies in an identified cohort of patients. And, thankfully, this is indeed receiving more attention, more study and, we can only hope, with time, improved outcomes. Recognizing the challenges physicians are facing as they anticipate or begin to build families, what can we do to build awareness and support our colleagues? We can start with our trainees, with education and infor-

mation and resources that many of us discovered along the way, during our career and family-building journeys. At UMass Chan Medical School, we are taking the first step to support our trainees by learning about the educational gaps. In an IRB-approved survey designed by a urology resident, Dr. Christine Van Horn, we are building a level of understanding of trainees’ experience regarding building families, and what gaps in both knowledge and support exist so we can begin to fill them. Dr. Van Horn reviewed the existing literature regarding these knowledge gaps, and the challenges faced by physicians, which mirror those outlined in Mroz’s article. Published literature explores issues such as the stigma of taking time off for pregnancy, barriers within institutions to pregnancy and motherhood for trainees, and duration of maternity leave afforded childbearing residents (2, 3, 4, 5). In addition to seeking information about the challenges faced when becoming pregnant and maintaining pregnancy, we sought also to understand other knowledge gaps, including fertility preservation options and the risks to the mother and fetus that can be unique to our careers. The study is ongoing, but preliminary review of the data has revealed findings, some of which are expected, and others which were more surprising. Interestingly, 56% of respondents felt some degree of guilt thinking about having children in residency and 51% were planning on delaying childbearing until completion of training. On knowledge base questions, the majority did not know basic information regarding oocyte cryopreservation and expressed uncertainty in knowledge of safety protocols for fluoroscopy use in pregnancy. In addition, 64% showed some concern regarding declining fertility while in training. The majority were also unsure of the answers regarding aspects of infertility in physicians or childbearing in training drawn from the primary literature with the exceptions of questions regarding bias or other negative aspects of pregnancy in training. As we continue to gather data from the survey, we ask ourselves where we go next with this information. We initiated this project with strong support from UMass Chan Medical School, and we will partner with our undergraduate medical students and graduate offices to provide educational resources for trainees. Based on these findings, we would like to focus on education surrounding the dynamics of fertility throughout training and offer additional information regarding fertility preservation options. These are topics which we, as physicians, often do not discuss with our trainees. However, we are poised as mentors, colleagues and educators to open the dialogue. We are excited to practice as residents and faculty during a time when these topics are gaining traction and looking forward to supporting our physicians and aspiring physician colleagues. + references (see digital edition)

Christine Van Horn, MD Urology Resident (PGY-4), University of Massachusetts Chan Medical School Jennifer Yates, MD Associate Professor and Vice-Chair of Academic Affairs, University of Massachusetts Chan Medical School, University of Massachusetts Medical Center Haley Schachter, third-year medical student, UMass Chan Medical School

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Infertility

Planned Oocyte Cryopreservation Armando Arroyo, MD Yanguang Wu, PhD

hat is planned oocyte cryopreserva-

tion? Who should consider oocyte freezing? When should they freeze oocytes? How many oocytes should be frozen? How are oocytes frozen? How effective is oocyte freezing? This short article discusses oocyte freezing for planned oocyte cryopreservation based on recent American Society for Reproductive Medicine guidelines. (1, 2) Planned oocyte cryopreservation is an approach that provides young, fertile women the option to conceive later in life when the ability to conceive naturally declines. This process involves ovarian stimulation, oocyte retrieval and oocyte freeze in liquid nitrogen. When a woman is ready, the oocyte is thawed, fertilized and the embryo is transferred to the uterus. The time to freeze oocytes is between the ages of 25 and 40, with the best time being before the age of 35. The ovaries are stimulated using the GnRH antagonist protocol. Usually, 20 oocytes are retrieved and frozen, depending on the woman’s age. The chance of having a child with frozen oocytes is dependent on the age of the woman and the number of mature oocytes cryopreserved. No increased birth risks have been identified compared to standard IVF. Planned oocyte cryopreservation, or OC , is effective and safe. In 2013, the American Society for Reproductive Medicine, or ASRM, recommended OC only for women undergoing gonadotoxic treatments seeking to preserve fertility. In 2018, the ASRM ethics committee stated: “planned OC is an emerging but ethically permissible procedure that may help women avoid future infertility.” (3) Many women are not aware the ability to naturally conceive declines with advancing maternal age. The Society for Assisted Reproduction, or SART, publishes yearly IVF outcome data. Women younger than 35 have a 50% chance of having a child with IVF on the first attempt, at 35-37 years (40%), 38-40 years (30%), 40-41 years (10%), 42 years (4%) and 45 years (1%). This fertility rate decline, when paired with age, is due to a decline in ovarian reserve. Human ovarian reserve – number of oocytes – declines from conception to menopause (Fig 1A). Number of oocytes drop dramatically from 6 million at 20 weeks gestation to

500,000 at birth, to 300,000 at menarche, to 25,000 at age 35, and 1,000 remain at age 50. Oocyte quality also declines with age, further reducing reproductive potential (Fig 1B). Oocyte quantity is important, however, oocyte quality may be even more important. What is the age-related master switch that determines oocyte quality? The definition of oocyte quality is the ability of an oocyte to mature, fertilize, cleave, implant and form a healthy infant. Surprisingly, after many years of investigation, very little is known about the master switch. Currently, the leading hypothesis is that oocyte chromosome ploidy is the major oocyte quality determining factor. Embryo ploidy is the best proxy marker of oocyte ploidy. The best information on embryo ploidy comes from preimplantation genetic testing of human embryos. Embryo aneuploidy dramatically increases with age: 20% at age 20, 50% at 35, 60% at 40, 80% at 42 and 90% at 44 (Fig 1B). Clearly, the decline in oocyte quantity and quality with advancing age reduces fertility potential. The oocyte freeze procedure is complex. The traditional procedure was known as the slow controlled-rate freezing technique. The first live birth from a cryopreserved human oocyte, in 1987, used the slow freeze technique. Slow freezing requires cooling the oocytes in low concentrations of cryoprotectants, or CP, slowly dropping the temperature at a rate of 0.3-2°C per minute until -196°C. The procedure normally takes 3-4 hours and requires expensive equipment . Besides the complicated manipulations and expensive costs, the oocyte survival, embryo development and live birth rates when using thawed oocytes in IVF were still significantly lower than using fresh oocytes. The unsatisfactory outcome of slow freezing is due to ice crystal formation that occurs during the slow cooling step which results in irreversible oocyte membrane damage. The cytoskeleton of the oocyte specifically spindle organization is impacted by the slow cooling rate. In 1998, a new technique, recognized at the beginning as fast-freezing, then changed to vitrification was deployed for oocyte freezing in clinical IVF. Compared to slow-freezing, vitrification is a fast freeze procedure. The oocytes are placed in high cryoprotectant concentrations, which replaces the water in the oocytes. Then they are directly deposited into liquid nitrogen. Because the temperature drops in a super-fast manner (greater than 25,000°C per minute), the remaining water molecules do not have time to form ice crystals, and instead instantaneously solidify into a glass-like structure. After 10 years of cryoprotectant modifications, replacing single CP with mixture of several CPs, and carrier-device liquid nitrogen changes, replacing closed systems with open systems, the vitrification technique became the preferred oocyte cryopreservation method by the end of the 2000s. (4) Today, planned OC by vitrification is routinely performed in IVF clinics. The IVF outcomes from vitrified oocytes are comparable to fresh retrieved oocytes as we described above. It seems vitrification perfectly resolved the problems of oocyte cryopreservation associated with the slow freeze method. Like all complicated embryology procedures, the success of oocyte vitrification requires support including a highly skilled, experienced embryologist and extremely strict laboratory procedure quality control. Academic fertility clinics have additional administrative, financial, clinical and research support all contributing to a successful oocyte cryopreservation program.

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

Planned Oocyte Cryopreservation Continued figs.

Infertility

1a, b

Planned OC is growing exponentially: 475 women froze their oocytes in 2009; 6,200 in 2015; and 10,000 in 2019. Oocyte freeze services are widely available, now provided by approximately 80% of the 480 IVF centers in the United States. Planned oocyte cryopreservation is an emerging procedure that may be considered by women concerned about age-related fertility loss. As with all newer technology, women need to be informed about the risks and benefits of this procedure. Women seeking this service should consider IVF centers with experience in oocyte vitrification. Each center’s live birth rate outcome is compiled by SART and available online. + references:

1. Practice Committees of ASRM, Mature oocyte cryopreservation: a guideline. Fertil Steril 2013, 99, 37-43 2. Ethics Committee of ASRM, planned oocyte cryopreservation form

women seeking to preserve future reproductive potential: An Ethics committee opinion, Fertil Steril 2018 3. Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline. Fertil Steril 2021 4. Practice committees of ASRM and Society of Reproductive Biologists Technologists (SRBT), A review of best practices of rapid-cooling vitrification for oocytes and embryos: a committee opinion, 2021

Armando Arroyo, MD, Associate Professor, UMass Chan Medical School, Medical Director of IVF, UMass Memorial IVF Center. UMass Memorial Health, Department of Reproductive Endocrinology and Infertility. Email: Armando.Arroyo@UMassMemorial.org. Yanguang Wu, PhD, Associate Professor, UMass Chan Medical School, Embryology Laboratory Director, UMass Memorial IVF Center. UMass Memorial Health, Department of Reproductive Endocrinology and Infertility. Email: Yanguang. Wu@UMassMemorial.org.

JANUARY / FEBRUARY 2022

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Infertility

Medications Used for In Vitro Fertilization Anna K. Morin, PharmD

n vitro fertilization, or

IVF, is a form of assisted reproductive technology, or ART, in which a woman’s reproductive system is stimulated to produce multiple oocytes, or eggs, which are extracted, fertilized in a laboratory and implanted in the uterus. (1) Since its introduction in the United States in 1981, 1.9% of all babies in the US are born through IVF and other ART. (2) IVF is the most effective option if natural or unassisted conception is not possible – i.e., either partner has received a diagnosis of unexplained infertility, fallopian tube damage or blockage, ovulation or uterine disorders, impaired sperm production or a genetic disorder. (1, 3) Protocols may differ depending on the woman’s diagnosis and individual IVF clinics, but IVF typically involves the following steps: oocyte production, oocyte retrieval, sperm retrieval, fertilization and embryo transfer. (1, 3) Oocyte production is a multistep process controlled by medications to replicate the different stages of ovarian stimulation and includes four main components: controlled ovarian hyperstimulation, suppression of ovulation, oocyte maturation and luteal phase support. (1, 3, 4) Each stage involves specific protocols and the most appropriate pharmacologic and therapeutic interventions are chosen after a thorough pretreatment evaluation. One full cycle of IVF takes approximately three to four weeks and begins with the use of medications on a precisely timed schedule to increase the number of mature follicles that develop in the ovaries and to control the time of ovulation. Many clinicians will prescribe a birth control pill for the woman to take for one or more weeks before beginning IVF to help prevent the release of hormones that could stimulate natural ovulation. (1, 3) Day one of the menstrual cycle is defined as the first day of menstruation. A baseline visit is typically scheduled for cycle day three and includes a pelvic ultrasound to measure follicle growth and bloodwork to measure hormone levels. (1, 3) If appropriate, injectable follicle stimulating hormone, or FSH, mediations; such as follitropin (Gonal-F®, Follistim®) urofollitropin (Bravelle®) and menotropins (Menopur®, Repronex®), can be started to stimulate development of multiple follicles and eggs in the ovaries. (3, 4) FSH medications need to be subcutaneously self-injected at a consistent time daily, typically in the evening, over seven to 12 days until multiple mature size follicles have developed. (1, 3) FSH agents should not be used in patients with primary ovarian failure and are contraindicated in patients with overt thyroid or adrenal dysfunction, pituitary tumors, abnormal uterine bleeding on unknown origins, ovarian enlargement (not due to polycystic ovary syndrome) or previous hypersensitivity to any of these agents. (3, 4) Common adverse effects include soreness or mild bruising at the site of injection, abdominal bloating, abdominal cramping, headaches and breast tenderness. The goal of IVF ovarian stimulation is to produce approximately eight to 15 quality eggs (about 15-20 millimeters in

diameter) for retrieval. (1, 3) Over stimulation of the ovaries can lead to significant discomfort and, in rare cases, ovarian hyperstimulation syndrome, or OHSS. (1, 3, 4) However, multiple eggs are often needed because some may not fertilize or develop normally following fertilization. Pelvic ultrasounds and blood testing is repeated every few days throughout the cycle and depending on the results of these tests, the dose of FSH may be adjusted up or down and other medications added as part of the IVF protocol.1,3 Pulsatile release of gonadotropin releasing hormone, known as GnRH, induces the production and release of luteinizing hormone, or LH, and FSH from the gonadotrophic cells of the anterior pituitary. (3, 4) At midcycle, a large increase in GnRH release results in an LH surge, that, in turn, induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization. GnRH agonist or GnRH antagonist products can be self-administered subcutaneously to suppress the pituitary gland’s ability to produce the LH surge needed for ovulation until the developing eggs are ready for retrieval. The GnRH agonist leuprolide Lupron® can be utilized to down regulate the pituitary gland’s ability to produce the LH surge. Referred to as the “long Lupron” or “luteal Lupron” protocol, leuprolide is usually started on day 21 of the menstrual cycle (about seven days before the next expected onset of menses), followed by the start of FSH medication within the first two to seven days after menses begins. (3) The leuprolide dose is often reduced when the FSH product is started. Instead of leuprolide, a GnRH antagonist such as cetrorelix (Cetrotide®) or ganirelix (Antagon®) can be used to prevent premature ovulation. (3) GnRH antagonists compete with native GnRH at pituitary binding sites, thus preventing the release of LH and FSH in a dose-dependent manner. Commonly administered subcutaneously, GnRH antagonists are started once the follicles have reached 14 millimeters, typically on or about the sixth day after initiation of FSH, and continued until human chorionic gonadotropin, or hCG, is started. (3) The effects of GnRH antagonists on LH and FSH are reversible after discontinuation of treatment. The “long Lupron” IVF protocol is commonly used, however, the GnRH antagonist protocols are now used more often. Success rates are similar with both protocols, and the use of ganirelix is associated with fewer injections during the stimulation cycle and lower risk for OHSS compared to the “long Lupron” protocol. (5)

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WORCESTER MEDICINE

Infertility

Medications Used for In Vitro Fertilization Continued

Human chorionic gonadotropin, or hCG, available as the brand name products Novarel®, Ovidrel® and Pregnyl®, replicates the effect of an LH surge. (3, 4) Administered as a subcutaneous or intramuscular injection when the follicle measurements reach 15-20 millimeters in diameter and one day after the last dose of a, FSH medication, hCG produces final maturation of the eggs in preparation for ovulation. (1, 3, 4) Regardless of the stimulation protocol used, the egg retrieval procedure is planned for 34-36 hours after hCG injection and before ovulation. (1, 3) Adverse effects of hCG include nausea, vomiting, abdominal pain, tiredness, edema, headache and injection site reactions. After egg retrieval, women may experience cramping and feelings of fullness or pressure. On the day of egg retrieval, progesterone may be started to make the uterine lining more receptive to embryo implantation. (1, 3, 4) Administered intramuscularly or as a vaginal insert (gel or suppository), progesterone is continued for a minimum of 30 days after pregnancy has been confirmed. Progesterone is associated with headache, breast tenderness, irritation, slight bleeding and vaginal irritation. Following egg retrieval and incubation, fertilization takes place using two common methods: conventional insemination, where healthy sperm and mature eggs are mixed and incubated overnight; or intracytoplasmic sperm injection, known as ICSI, where a single healthy sperm is injected directly into each mature egg. (1, 3) ICSI is preferred when sperm quality or number is low or if prior conventional fertilization attempts failed. One or more healthy fertilized eggs, now called embryos, can be implanted into the uterus three to five days after fertilization or may be frozen for use in a subsequent cycle. Prior to implantation, embryos can be tested to identify genetic or chromosomal defects. The success of an IVF cycle ending in a live birth depends on several factors, including the woman’s age, cause of infertility and treatment approach. (1, 2, 3) Chances of success increase when more than one cycle of IFV is done. The success rates of individual infertility clinics in the United States are published on the Assisted Reproductive Technology website – www.sart.org. Women and couples considering IVF should discuss the risks and benefits with their health care provider. Although IVF has a high rate of success, it comes with some disadvantages as well, including potential adverse effects of multiple infertility medications and associated invasive procedures, as well as an increased rate of multiple births – i.e., twins or triplets. In addition, IVF can be financially, emotionally and physically stressful. According to the National Conference of State Legislatures, the average cost of an IVF cycle in the U.S. is $12,000 to $17,000, depending on which tests are required, the type and dose of medication(s) used, and the number of cycles required to become pregnant (https://www.ncsl.org/research/health/insurance-coverage-for-infertility-laws.aspx). Insurance policies cover the cost associated with IVF in some states, although this varies depending on location and individual insurance policy. +

references:

1. In vitro fertilization (IVF). Mayo Clinic. Updated 9/10/21. Available at: https://www.mayoclinic.org/ tests-procedures/in-vitro-fertilization/about/pac20384716. Accessed: November 19, 2021. 2. CDC, Assisted Reproductive Technology Surveillance – US, 2017. MMWR 2020;69(9):120. Available at: https://www.cdc.gov/mmwr/ volumes/69/ss/ss6909a1.htm. 3. Advanced Fertility center of Chicago. Details about injectable medications for in vitro fertilization, IVF. Available at: https://advancedfertility.com/ ivf-in-detail/injectables-ivf-treatment/. Accessed: November 19, 2021. 4. Panesar K. Medications used for in vitro fertilization. US Pharm 2016;41(9):HS8-HS11. 5. Fluker M, Grifo S, Leader A, Levy M. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertility and Sterility 2021; 75(1):38-45.

Anna K. Morin, PharmD Associate provost – Worcester/Manchester Massachusetts College of Pharmacy and Health Sciences

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Infertility

Delaying Childbearing During Medical Training Gianna Wilkie, MD

t is well known that medical training is not

easy and is all encompassing of your time. Between medical school, residency and sometimes a subspeciality fellowship, seven to 12 years of a women’s reproductive life may be spent buried under books in medical libraries or working 80 hours a week dedicated to taking care of patients. Many medical residents cite concerns related to negative career repercussions, clinical duty coverage, board certification requirements and possible extended training as reasons for delaying childbearing. (1) Therefore, many female physicians may choose to delay pregnancy to pursue their career goals, putting them at increased risk of age-related adverse pregnancy outcomes including miscarriage and infertility. My personal experience is like that of thousands of female physicians across the country. I started medical school at the age of 22 and obstetrics and gynecology residency at the age of 26. I then decided to pursue a maternal-fetal medicine fellowship at the age of 30 and will finish my medical training at the age of 33. My husband is also in medicine and currently completing a three-year cardiology fellowship. While we have both always planned to have children, we have chosen to delay pregnancy until I am finished with my medical training, because no point in our training seemed like the “right time.” There was always another clinical experience or board exam in the future that seemed like a hurdle that we should complete before thinking about building a family. While I have never been told that pregnancy was not allowed during training, I have seen the struggles of my colleagues. They have taken short parental leaves to avoid extending medical training and often had to work every weekend leading up to their deliveries, and upon their return, to make up for their absence. While everyone tries to be supportive of their pregnancies, it creates significant scheduling difficulties and strain on their co-workers. Medical training is also a time of high-intensity immersion and learning, and I have seen my colleagues feel

personal guilt for missing clinical experiences and learning opportunities. While pregnancy is not discouraged, it’s uniquely challenging in medical training. As a maternal fetal medicine fellow, I deal with the complications of pregnancies complicated by advanced maternal age – 35 or older – daily. Therefore, the effects of delayed childbearing, including preterm birth, are not lost on me. The struggle between being ready to have children, achieving my career aspirations and avoiding the negative consequences of a pregnancy associated with advanced maternal age are definitely present. Given 65% of physicians reported concerns about future fertility, I know I am not alone in my feelings. (2) Many medical professionals have sought options to stop the aging ovarian clock by, for example, pursing oocyte cryopreservation. While I have not personally done this, many of my colleagues have and maybe I missed my window of opportunity. However, the process of undergoing oocyte cryopreservation is not easy and is also time consuming, which may not seem feasible to medical trainees either. As I reach the midway point of my fellowship, I have started to think about whether or not there will ever be a right time to be pregnant. I see many female physicians balancing successful careers and life at home giving me hope for the future. + references

1. Willett L, Wellons M, Hartig J, Roenigk L, Panda M, Dearinger A, Allison J, Houston T. Do Women Residents Delay Childbearing Due to Perceived Career Threats? Academic Medicine 2010; 85(4): 640-646. 2. Nasab S, Shah JS, Nurudeen K, Jooya ND, Abdallah ME, Sibai BM. Physicians attitudes towards using elective oocyte cryopreservation to accommodate the demands of their career. J Assist Reprod Genet 2019; 36(9): 1935-1947. Gianna Wilkie, M.D. Maternal Fetal Medicine Fellow University of Massachusetts Chan Medical School

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

From the Curator

The Birth and History of IVF (adapted from RMA Associates, New Jersey) B. Dale Magee, MD

rom the moment it began , infertility

treatment has been a story of technology advancing in front of medical ethics. Issues of consent, genetic engineering, fertility rights and system financing priorities have been, and continue to be, at least as challenging as the technology. For this issue, I present you with a history of infertility treatment published online by Reproductive Medicine Associates of New Jersey. You may be surprised to learn that the birth of in vitro fertilization, or IVF, was not in this century but rather began in the 1800s. The story of IVF may sound like it’s written for a science-fiction novel but in truth is well documented in prestigious medical journals. The story of IVF in the U.S. marks the beginning of millions of babies born through technology and advanced reproductive procedures, each one making their historical mark on our great nation.

the

1800s

In the mid 1800’s, scientists finally discovered that pregnancies occurred from a combination of sperm and egg. Prior to that time it was not understood why semen caused conception and what women produced that allowed for pregnancy. Shortly after that discovery, Dr. [J. Marion] Sims at the Women’s Hospital in New York performed a fresh intrauterine insemination from the husband’s sperm. This created one pregnancy that ended in miscarriage. Fertility treatment mostly consisted of gynecological surgery at that time. In 1884 Dr. William Pancoast in Philadelphia performed the first donor insemination using sperm from the medical student voted “best looking” in his class. It was anonymous, and both the husband and wife were not even informed that a donor was being used until years later. Luckily, the husband was elated; however this dishonesty and lack of informed consent would not be acceptable today. the early

1934 Gregory Pincus performed IVF-like research on rabbits but was fired from Harvard due to his controversial research. His top researcher Menkin was hired by Dr. Rock in New York and began human IVF research. At Columbia Hospital down the street in New York in 1951, Dr. Landrum Shattles used the Rock-Menkin protocols to duplicate the experiments. In 1965, at Baltimore’s hospital, Dr. Jones worked with Dr. Edwards of England and fertilized the first human egg in vitro. In 1968 back in England, Dr. Edwards joined Dr. Patrick Steptoe and used a Laparoscopy surgery to retrieve an egg and fertilize it in vitro (in the lab). They published the results in the journal Nature in 1969. The political opinion of IVF and governmental regulations of research were still evolving. More Americans were accepting of the concept but the Pope was adamantly opposed. the

1970s

On September 12, 1972 at 8 a.m., a surgery was taking place in a hospital in Brooklyn. Dr. William Sweeney retrieved five eggs from a female. The woman’s husband took the eggs in a taxi five miles across town to give them to Dr. Shettles at Columbia-Presbyterian Hospital. The husband then went into a collection room and produced a fresh ejaculate to be used to fertilize the eggs. By 2 p.m. the hospital chairman learned about the experiment and forbid the embryos to be transferred back to the mother. The husband was informed at 4 p.m. that evening and the wife was informed by 9 p.m. while she was still recovering from surgery. This would have been the first case of IVF with embryo transfer but it was stopped prematurely. Three years later in England in 1975, Drs. Edwards and Steptoe announced the first successful pregnancy created from IVF; however it ended in and ectopic pregnancy. But by 1978, the first successful live birth from IVF was announced by Drs. Edwards and Steptoe in England. Lesley Brown gave birth to her daughter, Louise Joy Brown, who was healthy in every way. While the birth of a test tube baby shocked the watching world, it had been a century in the making. the

1980’s and 1990’s

After wading through more regulatory hurdles, the first U.S. IVF clinic was opened by doctors [Howard and Georgeanna] Jones in Virginia. The race was on but Australia was the second country to announce a test tube baby in 1980. The U.S. announced the birth of IVF baby Elizabeth Carr in 1981 (1). + reference:

1900s

In the early 1900’s much research was done on hormones and how they related to fertility. The first infertility clinic opened in 1926 in Massachusetts. In

1. RMA, The Birth and History of IVF, accessed online 10/14/21, https://rmanetwork.com/blog/birth-history-ivf/

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WORCESTER MEDICINE

Legal Consult

States of Emergency Peter Martin, Esq.

“[The forefathers] knew what emergencies were, knew the pressures they engender for authoritative action, knew, too how they afford a ready pretext for usurpation. We may also suspect that they suspected that emergency powers would tend to kindle emergencies.” (1)

ov. gharlie baker declared a state of emergency in massachusetts

on March 10, 2020, resulting from the COVID-19 pandemic, citing Massachusetts General Laws chapter 17, section 2A and chapter 639 of the Acts of 1950 (the “Civil Defense Act”). The governor on May 28, 2021 both rescinded his earlier declaration, and declared this state of emergency terminated as of June 15, 2021, with respect to both statutes. Thirty minutes later, he declared that “an emergency exists that is detrimental to the public health in the Commonwealth” as of May 28, 2021, under MGL c. 17, section 2A and not under the Civil Defense Act. The net effect of these twin declarations was to vest in the commissioner of public health the authority, with the approval of the Public Health Council, to extend or adopt measures to respond to the pandemic. The commissioner on June 14, 2021 re-issued, among other things, 14 public health orders related to the pandemic, under what was referred to in some Department of Public Health documents as the “Modified Public Health Emergency” declared May 28, 2021. This sequence of events, and the legal authorities cited, raise interesting questions about what is a public health emergency and how do we know when it is over. Under what circumstances should the normal legal constraints on the exercise of governmental power be loosened and what can a government not do during an emergency? As the COVID-19 pandemic, hopefully, evolves into an endemic respiratory disease like the annual flu, the modified public health emergency should likewise evolve into something else, but what, and when and why? The two statutes cited by Gov. Baker vary widely in intent and scope. The 1950 law is clearly a relic of the Cold War; section 5 of that statute, which conferred on the governor the power to “issue a proclamation or proclamations setting forth a state of emergency,” begins by citing “the existing possibility of the occurrence of disasters of unprecedented size and destructiveness resulting from enemy attack, sabotage or other hostile action.” The trigger for such a proclamation is “the occurrence of any disaster or catastrophe resulting from attack, sabotage or other hostile action or by fire, flood, earthquake or other natural causes.” The scope of the governor’s powers under section 7 of the law is extremely broad: “the governor, in addition to any other authority vested in him by law, shall have and may exercise any and all authority over persons and property, necessary or expedient for meeting said state of emergency, which the general court in the exercise of its constitutional authority 16

may confer upon him as supreme executive magistrate of the commonwealth and commander-in-chief of the military forces thereof.” The statute is silent as to the length of an emergency proclamation and contains no provisions for review, renewal or rescission of such a proclamation. The second statute cited is far narrower. It governs the powers of the public health commissioner in certain circumstances. It states: “upon declaration by the governor that an emergency exists which is detrimental to the public health,” the commissioner, with the approval of the governor and the Public Health Council, may take such actions as “he may deem necessary to assure the maintenance of public health and the prevention of disease.” This statute is silent as to under what circumstances the governor may declare the existence of an emergency that is detrimental to the public health, and it does not provide for either time limits or periodic review of an emergency declaration. This silence is typical of many state statutes regarding public health emergencies. Where a state law is silent on what constitutes a public health emergency, it generally permits the governor to make that determination in his sole discretion. Where a state law seeks to define “public health emergency” it does so with broad language; many states adopt language derived from The Model State Emergency Health Powers Act proposed in 2002 by the National Conference of State Legislatures. The Model Act definition of public health emergency is “an occurrence or imminent threat of an illness or health condition that is believed to be caused” by a number of events, including bioterrorism, a natural disaster or “the appearance of a novel or previously controlled or eradicated infectious agent or biological toxin” that poses a high probability of a range of harms, from a large number of deaths or serious or long-term

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Legal Consult

States of Emergency Continued

disabilities, to the “widespread exposure to an infectious or toxic agent that poses a significant risk of substantial future harm to a large number of people” in the affected population. The breadth of this definition is understandable, if not terribly useful in distinguishing between serious public health concerns and “emergencies.” The lack, or the breadth, of statutory guidance as to what constitutes a public health emergency is perhaps inevitable given the evident need to respond quickly to unanticipated and serious threats. However, that flexibility can lead to questionable invocations of authority, as when Gov. Deval Patrick declared in 2014 that the state’s opioid addiction epidemic was a public health emergency. That action prompted an article in The New England Journal of Medicine (2) in which the authors questioned whether Gov. Patrick’s actions met what the authors considered the “three key criteria” for declaring a public health emergency. They are: “the situation is exigent, the anticipated or potential harm would be calamitous, and the harm cannot be avoided through ordinary procedures.” Are any of widespread opioid addiction, or rampant gun violence, or chronic conditions such as obesity, or an enduringly high rate of traffic fatalities, a public health emergency justifying suspension of due process and legal protections? The problem of finding a public health emergency in garden-variety health problems is exacerbated by the lack of a clear path out of emergency and into resumed normality. The Model State Emergency Health Powers Act permits the governor to terminate the public health emergency by executive order; limits emergency declarations to 30 days, but permits the governor to renew declarations for an unlimited number of additional 30-day periods; and gives the legislature the power to terminate the declaration but only with a majority vote of both chambers. It is worth noting, the federal National Emergencies Act (50 U.S.C. sec. 1601 et seq.) does not define “national emergency” and permits such emergencies to continue so long as the president annually notifies Congress the emergency continues. Since the enactment of the NEA in 1976, there have been 72 executive orders declaring emergencies, beginning with an order blocking Iranian government property in 1979; of those executive orders, 41 remain in effect (3). Both the Model Act and the NEA suggest regardless of whether the term emergency is adequately defined, statutory guardrails can be set up to ensure emergency declarations are time-limited and periodically reviewed. It appears convincing the public a COVID-19 public health emergency continues may be getting harder. People objecting to vaccine mandates sometimes point to the fact that, so far, COVID-19 vaccines have received only “emergency use authorization” from the FDA which they argue legally permits vaccine refusal. The recent decision by the Fifth Circuit Court of Appeals regarding a proposed “emergency temporary standard” from the Occupational Safety and Health Administration, or OSHA, rests in part on citing stringent statutory language permitting an ETS to be promulgated only when exposure to hazards places workers in grave danger and the ETS is necessary to alleviate employees’ exposure to that grave danger. In the face of growing resistance to emergency measures and the absence of specific statutory or other guidance, when is it appropriate for a governor to rescind a public health emergency declaration?

It appears Gov. Baker’s May 28 actions were a measured step away from the extraordinary “civil defense” powers conferred on him by the Civil Defense Act and toward the more limited and consultative exercise of power, in conjunction with the Public Health Council and the commissioner of public health, oriented specifically to “the maintenance of public health and the prevention of disease.” What remains unclear is what the next step may be, and how it will be justified. Statutory guidance on the length of a governor’s public health emergency declaration and some requirement for periodic review of that declaration by third parties would provide a clearer path from pandemic emergency steps to normal public health measures. The lack of definitive statutory guidance in emergency situations may make that next step less a matter of epidemiology and more a matter of political calculation. Gov. Baker appears to be doing his best to exercise his powers responsibly, but in the absence of clear standards and procedures governing “public health emergencies,” Justice Jackson’s concerns remain. + Peter Martin, Esq., is a partner at Bowditch and Dewey. He concentrates his practice on health care law, representing hospitals, long-term care facilities, physicians and other facilities and providers facing complex regulatory and contractual issues throughout Massachusetts and beyond. references:

1. Youngstown Sheet & Tube Co. v. Sawyer, 343 U.S. 579, 650 (1952) (Justice Jackson, concurring) cited in Elsea, J., “Definition of National Emergency under the National Emergencies Act,” Congressional Research Service Legal Sidebar (March 1, 2019). 2. Haffajee, R., Parmet W. and Mello, M., “What is a Public Health ‘Emergency’?”, NEJM vol. 371, no. 11, p. 986. 3. See Brennan Center for Justice, “Declared National Emergencies Under the National Emergencies Act” (updated November 10, 2021).

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WORCESTER MEDICINE

As I See It

Universal Newborn Home Visits Sheilah H. Dooley, RN, BSN, MS

Service, we recognize newborns do not come with an owner’s manual. Caring for a newborn is challenging under the best of circumstances. Traditional prenatal and pediatric care is often based on the assumption that parents have the basic knowledge and resources to provide a nurturing, safe environment and provide for the emotional, physical, developmental, and health care needs of their infants and young children. Unfortunately, many low-income, at-risk families encounter barriers to basic health care, may face food insecurity and have insufficient knowledge of parenting skills and an inadequate support system of friends, extended family or professionals to help. Pernet’s Maternal and Child Health Program began serving Worcester mothers and newborns in 1955. More than 200 people are served by this program each year. The program has grown from basic infant care and parenting skills training to a robust menu of assistance in navigating the world with a newborn. We offer nursing care for medically complex infants in the home, screen for developmental delays, and make referrals linking parents to the support they need and the child to the services they may require to thrive. Maternal Child Health visits have significant impact preventing newborn hospital readmissions; protecting against preventable childhood diseases through immunizations and regular medical care; preventing developmental delays or long-term consequences of unaddressed developmental delays; preventing child abuse and neglect; and addressing early, root causes for remedial education and juvenile delinquency. State law mandates a new mother receive a home visit if she went home within 48 hours of giving birth, but the city of Worcester lacks the capacity to ensure all eligible mothers receive such a visit. For an at-risk mother, this specialized care is a chance to break the cycles of poverty, violence and diminished opportunities. While much evidence points to the positive impact home visits have on at-risk mothers and newborns, there is equally compelling data that all mothers, regardless of socioeconomic status, home environment, or presence of risk factors, benefit tremendously from a newborn home visit. The physical and mental health and wellbeing of the mother is improved with these visits as well.

t pernet family health

The City of Worcester’s Community Health Improvement Plan calls for investment in early assessment and intervention services. Worcester Health Babies Collaborative, Together for Kids Coalition and other community partners have worked to improve outcomes for at-risk newborns and questioned what more can be done. Forums held in conjunction with Clark University, Greater Worcester Community Foundation and Early Intervention programs have explored early childhood mental health. There is continued support for devising a continuum of care for all newborns so they have the best possible start in life. There has been examination of this topic in Worcester, but no comprehensive strategy had emerged – until now. In response to this evidence, as well as compelling local need, Pernet has joined forces with community partners – The Worcester Healthy Baby Collaborative, Family Health Center of Worcester, and Edward M. Kennedy Community Health Center – to design and implement a Universal Newborn Home Visit program, to ensure all Worcester newborns are visited. A grant from the Worcester Together Fund’s Reimagining Phase has been an early catalyst for this work. Our goal is for all Worcester mothers and newborns, regardless of circumstance, culture, socio-economic status or background, receive a home visit within the first two weeks of the infant’s life. That visit will be a source of reassurance and comfort or a lifeline to supportive services and intervention, depending on the child and mother’s needs. This program will grow over time into a sustainable resource that any Worcester mother can count on. While the program is in its early stages, Pernet continues to make home visits based on referrals from the UMass Memorial Newborn Nursery and St. Vincent Hospital. Funding and the challenge of recruiting qualified staff make expanding this program a slow, but steady process. In the near future, the partner agencies will recruit, train and support a sufficient number of family health advocates to make visits to all newborns in the City of Worcester within the first month of life. Our team will provide culturally appropriate support and supervision around basic infant care, parenting, appropriate parenting skills, coaching for breastfeeding mothers, screen for postpartum depression, and impart the importance of regular medical follow up for both mother and child. These visits will provide lasting, longterm change to the way all new parents are supported, in particular those who experience risk factors. Connecting families with supportive resources from the very beginning supports the health of a baby during the first year of life and can prevent developmental and behavioral problems at a later stage. Teaching parents the skills necessary for positive parenting early, enhances the child’s emotional and educational advancement. A healthy start makes all the difference. There is universality to this program. All families need support in some way. This program will make significant strides in improving maternal health, promoting good parenting practices and ensuring every one of the nearly 2,500 babies born to Worcester mothers each year has the chance to have a healthy start. “A baby’s health is the community’s wealth,” said former Commissioner of Health and Human Services Leonard Morse. Infant mortality is a mirror on the community. Universal Newborn Home Visits are a start to having healthy babies, healthy families and a healthy community. + Sheilah H. Dooley, RN, BSN, MS, is the Executive Director of Pernet Family Health Service in Worcester, a graduate of Boston College School of Nursing, Affiliate Faculty at the University of Massachusetts Chan Medical School Graduate School of Nursing, and the Clerk of the Board of Directors of the United Way of Central MA.

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Society Snippets WORCESTER DISTRICT MEDICAL SOCIETY 2021 FALL DISTRICT MEETING & AWARDS CEREMONY Dr. A. Jane Fitzpatrick Community Service Award Recipient

WDMS Career Achievement Award Recipient

Kavita Babu, MD

Thomas F. Halpin, MD

WDMS 2021 SCHOLARSHIP AWARD RECIPIENTS

Alec Allain University of Massachusetts Chan Medical School

Kendall Burdick University of Massachusetts Chan Medical School

Catherine Cattley University of New England College of Osteopathic Medicine

Allison Chevalier New York Institute of Technology, College of Osteopathic Medicine

Stephanie Craig Lake Erie College of Osteopathic Medicine

Brennan Dagle University of Massachusetts Chan Medical School

Arianna Gray Philadelphia College of Osteopathic Medicine

Tara Hebert University of New England College of Osteopathic Medicine

Tamika Isaac Philadelphia College of Osteopathic Medicine

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Zain

Chaudry The Robert Larner, MD, College of

Kelly Flanagan University of Massachusetts Chan Medical School

Laura Knapik University of New England College of Osteopathic Medicine

WORCESTER MEDICINE

Society Snippets WDMS 2021 SCHOLARSHIP AWARD RECIPIENTS (continued)

Dhanya Kumar University of Massachusetts Chan Medical School

Siena Romano Georgetown University School of Medicine

Cindy Le University of Massachusetts Chan Medical School

Juliet Ross Albany Medical College

Rebecca Toohey University of Massachusetts Chan Medical School

Ashwin Panda University of Massachusetts Chan Medical School

Amanda Scudder New York Medical College

ToQuynh Vu University of New England College of Osteopathic Medicine

Marc Poirier Lake Erie College of Osteopathic Medicine

Nathan Taber University of Massachusetts Chan Medical School

Mina Zaky Tufts University School of Medicine

Please Help Support the Next Generation of Physicians It is your generous support that makes this scholarship program possible every year. Your tax deductable contribution, in whatever amount, will allow us to continue this WDMS tradition of giving to help support the next generation of physicians. Visit our website: www.wdms.org and click the green box.

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

In Memoriam

Dominic J. Nompleggi, MD, PhD

t i s w i t h h e a rt f e lt s a d n e s s t h at w e n o t e t h e pa s s i n g o f

Dominic Nompleggi, MD, PhD. Dom was a staff member of the University of Massachusetts (now Chan) School of Medicine and UMass Memorial Medical Center for 30 years, serving initially as its Director of the Adult Nutritional Support Service and the Director of Esophageal Motility Laboratory. In 2000, he became the Clinical Chief of UMMC’s Gastroenterology Division until 2004 when he became the Chief of the Division, a position he notably and faithfully served until his passing Aug. 27, 2021, surrounded by his beloved wife, Ann and their two daughters, Victoria, “Tori,” and Elizabeth, “Libby.” Dom was born in Boston in May 1950. Following his graduation from Boston College High School in Dorchester, Mass., Dom spent the next 14 years at Georgetown University earning a plethora of degrees including a BA, MS, PhD, and an MD. He then returned to Boston completing his residency at the New England Deaconess Hospital where he also served as Chief Medical Resident from 1985 to 1986, becoming a member of the Harvard Medical School faculty. After a research fellowship in Nutrition at the New England Deaconess Hospital, Dom completed a clinical and research fellowship at Brigham and Women’s Hospital before accepting an invitation to join the faculty of the University of Massachusetts Medical School and the Gastroenterology Division of the University of Massachusetts Medical Center in 1991. Dom was the proverbial triple threat. His research interests centered around the mechanisms of stress-related mucosal damage to the gastrointestinal tract and nutritional support of the hospitalized patient. He authored numerous papers and book chapters on these subjects and was invited to lecture on these topics both regionally and nationally. Dom was an award-winning teacher. He helped to organize and implement the Physician, Patient, and Society Course, which for many years was a requirement for UMass medical students. Whether teaching medical students, medical residents, gastrointestinal fellows or colleagues, Dom was insightful, calm, unpretentious and frequently interjecting a gentle humor into his discussion. Above all, Dom was a consummate physician: intelligent, knowledgeable, caring, allowing himself always to be present with his patients. Dom cared for the person while treating the disease. Despite being perpetually listed among the Best Doctors in America since the award’s inception, Dom remained a humble and self-effacing physician who delighted in caring for his patients.

During his tenure as Chief of the Division of Gastroenterology, Dom successfully gathered around himself a group of outstanding gastroenterologists and hepatologists, fostered a collegial relationship with his community colleagues, helped create a nationally acknowledged excellence in diagnostic and therapeutic endoscopy, and successfully steered the GI division through administratively challenging times. Dom’s gifts facilitated him to become a successful leader. Simply stated, he cared. When negotiating or in a discussion, Dom sought to listen and understand the other person’s point of view, which helped him create common ground for agreement. When in his presence you sensed his concern for your welfare. Dom was a peacemaker. Dom, like most gastroenterologists, loved good food and drink, especially martinis. He loved music, the beauty and peacefulness of the Rhode Island shore, and the time spent with his family there or on Amelia Island off the Florida Coast. While Dom loved being a physician, he cherished even more time his family – Ann, Tori and Libby. When with him ,the conversation would often drift to what the three women in his life were accomplishing. He was a proud husband and father. Dom’s prolonged exposure to the faith of his Italian mother and father, and the teaching of the Jesuits at Boston College High School and Georgetown University, led him to view life and his talents as a gift to be used for a purpose. As his life journey progressed, Dom found his purpose in being the beloved husband of Ann, the beloved father of Tori and Libby, and a beloved physician to his patients, and colleague to his peers. Well done, Dom. Well done, good and faithful servant. Thank you to an esteemed friend and colleague, John Zawacki, MD +

JANUARY / FEBRUARY 2022

WORCESTER MEDICINE

Complete Infertility Care Now Offered Locally The new UMass Memorial Health in vitro fertilization (IVF) center and fully certified embryology laboratory provides state-of the-art comprehensive services for the communities of Central Massachusetts. It’s the only fertility center providing complete IVF services locally. The IVF unit is in the Levine Building adjacent to UMass Memorial Medical Center – Memorial Campus. Fertility services are provided by highly experienced physicians and staff.

Assisted Reproductive Technology (ART) The center provides many assisted reproductive technology services, including intrauterine insemination, IVF, intracytoplasmic sperm injection, blastocyst culture and embryo cryopreservation. The clinical team is composed of experienced fertility professionals: • Reproductive endocrinologists who are double board certified by the American Board of Obstetrics and Gynecology in reproductive endocrinology and infertility: • Armando Arroyo, MD, IVF Center Medical Director • John Yeh, MD, Director, Division of Reproductive Endocrinology and Infertility • Shaila Chauhan, MD • AAB certified experienced embryologist Yanguang Wu, PhD, HCLD, Embryology Laboratory Director • Anesthesiologists • Experienced IVF nurse coordinators

Male Infertility Katherine Rotker, MD, is the only fellowship fertility trained urologist in Central Massachusetts and leads the male fertility program. She provides consultations, Percutaneous Epididymal Sperm Aspiration (PESA), Testicular Sperm Aspiration (TESA) and micro TESA. The Urology Clinic is located adjacent to the Fertility Clinic in the Levine Building.

Preimplantation Genetic Testing (PGT) Our center provides embryo genetic testing for embryo aneuploidy, monogenetic disorders (i.e., cystic fibrosis, structural rearrangement translocations). The embryo biopsy is performed by embryology laboratory director Dr. Wu. We also offer DNA analysis by next generation sequencing which is performed by PGT certified laboratories and on-site genetic counseling by ABMG certified clinical geneticists and certified genetic counselors.

Egg Freezing The center provides elective egg freezing for women seeking fertility preservation for cancer and planned oocyte cryopreservation. Egg freezing by vitrification is performed in our embryology laboratory.

Fertility Preservation for Cancer Fertility preservation services for female and male cancer patients are available. Vitrification of sperm, testicular tissue and oocytes are performed in our embryology laboratory. Ovarian tissue cryopreservation will be available soon. A third-party reproduction program, including donor eggs and surrogacy, will be available soon. For further information, please call 508-334-1345.

JANUARY / FEBRUARY 2022

INTRODUCING OUR NEW IVF CENTER. Complete infertility care now offered locally.

The path to pregnancy can be overwhelming. Your patients need an expert team with the right experience and capabilities. That’s why we’re pleased to announce the addition of our on-site IVF Center to round out our robust fertility services — ensuring convenient, state-of-the-art care, close to home. Call 508-334-1345 to speak to one of our infertility specialists.

For referrals, call Physician Concierge Services at 800-431-5151.

Worcester Medicine January/February 2022

Articles inside

Dominic J. Nompleggi, MD, PhD

Universal Newborn Home Visits

States of Emergency

The Birth and History of IVF

Delaying Childbearing During Medical Training

Medications Used for In Vitro Fertilization

Planned Oocyte Cryopreservation

Building Families: Educating our Next Generation of Physicians

An Infertility Story: One Woman’s Experience

Infertility/Decreased Fertility: Significant Positive Changes in the Last 30-40 Years

President's Message

Editorial