The Reproductive Endocrine Associates of the Massachusetts General Hospital: Fifteen Years of Integrated Clinical Practice and Investigation
Stephanie B. Seminara,
Janet E. Hall,
Ann E. Taylor,
William F. Crowley, Jr. and
Kathryn A. Martin
Reproductive Endocrine Unit, Department of Medicine, Massachusetts
General Hospital, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Dr. Stephanie B. Seminara, Reproductive Endocrine Unit, BHX 505, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114.
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Introduction
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The Reproductive Endocrine Associates is the
clinical practice of the Reproductive Endocrine Unit, a division of the
Department of Medicine of Massachusetts General Hospital (MGH). Founded
in 1984, the Reproductive Endocrine Associates is focused on providing
superior care to patients with a broad range of reproductive disorders.
Moreover, because of its setting within a multidisciplinary research
unit, the primary goal of this practice is to translate basic and
clinical research insights to patient care as quickly as possible. This
article aims to explore both facets of this unique practiceboth as a
reproductive endocrinology practice and as an integral link within an
interdisciplinary research unit.
The Reproductive Endocrine Associates is composed of seven
endocrinologists (six female, one male), all Board-certified in both
internal medicine and endocrinology and metabolism. Patients are also
seen by Clinical Fellows precepted by staff physicians in patient care
sessions held daily and one evening per week. The physical layout of
the clinic (861 ft2) includes one consultation room, two
examination rooms, an ultrasound suite, and a teaching/coordination
area for patients undergoing ovulation induction. The practice space is
one floor below the administrative and professional staff offices,
conference room, and research laboratory of the Reproductive Endocrine
Unit. The close proximity of the clinic practice to the research space
provides seamless professional continuity for the seven staff
physicians, each of whom directs his/her own clinical research program.
Patients are easily introduced to the newest protocols and therapeutic
trials being conducted within the Unit. Although out-patient aspects of
clinical investigation do take place within the practice space, almost
all in-patient protocols are executed in the Mallinkrodt General
Clinical Research Center (GCRC) on the MGH campus. The GCRC is a
seven-bed, NIH-funded facility that is an invaluable resource for
detailed studies of human reproduction.
The Reproductive Endocrine Associates has approximately 3200
patient-visits/yr. Over the past 15 yr, the number of patient-visits
has increased 10-fold, and the faculty has doubled in size. For this
uniquely situated practice, the largest percentage of new referrals
comes from primary care physicians (41%). Nine percent are from other
endocrinologists within the hospital, the Boston area, or around the
world. Thirteen percent of patients are self-referred. The remainder of
referrals derive from a variety of subspeciality services. Eighty-nine
percent of the patients seen over the past 3 yr are female; 11% are
male. The most common diagnostic categories seen within the practice
include hyperandrogenic syndromes, hypergonadotropic hypogonadism, and
hypogonadotropic hypogonadism (Fig. 1
).
The percentage of patients carrying specific diagnoses within each of
these broad categories is summarized in Table 1
. Due to the research interests of the
Unit, patients with relatively rare diagnoses, including precocious
puberty and virilizing ovarian/adrenal tumors, are also seen on a
regular basis.
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Interfaces within a multidisciplinary research network
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The Reproductive Endocrine Unit, at its core, is a tightly
interwoven collection of interdisciplinary research teams including
Female Physiology, Male Physiology, Biochemistry, Genetics, and Assay
Development. Although research interests span a wide spectrum from
basic biology to clinical investigation, traditionally the Unit has
focused on studies in humans. Each of the Reproductive Endocrine
Associates staff physicians either leads or participates in one or more
clinical research teams. Team meetings represent the cornerstone of
intellectual activity within the Unit; hypotheses are first formulated
and refined, protocols intensively reviewed and modified, primary data
discussed, and publications planned.
Although other medical centers may use similarly integrated approaches
to clinical care, the Reproductive Endocrine Unit is one of only two
National Centers of Infertility Research funded by the NICHD and has
received 10 yr of continuous funding. The broad goals of the Center
currently are to understand 1) the intrafollicular environment in
polycystic ovary syndrome (PCOS), 2) the role of gonadal proteins in
determining fertility, 3) the control of FSH secretion, and 4)
molecular defects in gonadotropin biosynthesis. These goals are
integrated with the other "partner" National Center at 5-yr
intervals. Therefore, different styles and approaches, representing the
best reproductive science from two institutions, can be brought to bear
on a single problem.
In addition, the Reproductive Endocrine Unit is the coordinating
base of the Harvard-wide Reproductive Sciences Center, 1 of 17 Centers
of Excellence also funded by the NICHD. This award is competitively
bestowed upon research institutions that have established a critical
mass of interdisciplinary investigators in reproductive biology.
Composed of 28 investigators with 38 NIH grants, the Center provides
critical core laboratories, consultations by core laboratory directors,
and a Harvard-wide educational series in reproduction. Therefore,
whether within the Reproductive Endocrine Unit, the National Center for
Infertility Research, or the Reproductive Sciences Center, the
clinicians of the Reproductive Endocrine Associates can avail
themselves of a tremendously rich research network (Fig. 2
).

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Figure 2. Relationship of the Reproductive Endocrine
Associates to the Reproductive Endocrine Unit, National Center for
Infertility Research, and the Reproductive Sciences Center.
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Typical cases: bench to bedside transitions
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Some of the most important contributions of the Reproductive
Endocrine Unit over the past 2 decades include 1) the development of
GnRH analogs for the treatment of precocious puberty, now the standard
of care worldwide (FDA approved), 2) the optimal use of pulsatile GnRH
to induce ovulation in women (similarly FDA approved) and sexual
maturation in men with endogenous GnRH deficiency, 3) the use of GnRH
analogs as a medical therapy for uterine leiomyomata, 4) the definition
of the neuroendocrine defects in PCOS, 5) the elucidation of the
physiology of the gonadal proteins (inhibin, activin, and follistatin),
and 5) the exploration of genotype/phenotype correlations in a variety
of reproductive disorders. None of these advances would have been
possible without committed patients who have been invaluable
collaborators in the research process. The following sections describe
some typical cases seen in this practice. They are selected not to
focus on specific management points per se but, rather, to
illustrate the practices bench to bedside philosophy, a dynamic frame
of reference that transforms a patients clinical presentation to an
investigative question.
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Case I
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MO is a 30-yr-old woman who originally presented as an adolescent
with primary amenorrhea and was told she would not be able to have
children. Since then, she had been maintained on conjugated estrogen
and progesterone therapy. When she was interested in fertility, she
presented to the Reproductive Endocrine Associates for a second
opinion. Her evaluation was notable for a history of 1) normal
adrenarche, 2) low gonadotropin levels and a lack of a gonadotropin
response to a single dose GnRH test but otherwise normal endocrine
axes, 3) normal brain imaging, and 4) an inability to smell.
To understand the pathophysiology of hypogonadotropic states, the
Reproductive Endocrine Unit has employed a tandem approach, studying
both normal subjects and those with an absent program of endogenous
GnRH secretion. Primate studies were the first to demonstrate that GnRH
is secreted in a pulsatile fashion from the hypothalamus (1). Due to
the short half-life of GnRH, LH and free
-subunit have been used as
markers of GnRH secretion in the human. Within the Reproductive
Endocrine Unit and the GCRC, hundreds of frequent sampling studies
(every 510 min) have been performed to create robust normative
databases of hypothalamic GnRH frequency at different stages of male
and female development and across different stages of the menstrual
cycle (Fig. 3
). These studies have
ultimately permitted an understanding of the spectrum of neuroendocrine
abnormalities in patients with reproductive disorders. Frequent
sampling studies in patients with hypogonadotropic hypogonadism (with
or without anosmia) have allowed the identification of discernible
abnormalities of GnRH secretion, including a complete absence of GnRH
pulsatile activity, enfeebled but present LH pulses, and other abnormal
patterns (2).

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Figure 3. Dynamics of pulsatile LH secretion in the
early, mid-, and late follicular phases (EFP, MFP, and LFP), during the
midcycle surge (MCS), and the early, mid-, and late luteal phases (ELP,
MLP, and LLP) in normal women. Note the increase in LH/GnRH pulse
frequency through the midfollicular phase, the dramatic increase in LH
amplitude at the midcycle surge, and the slowing of the GnRH pulse
generator through the luteal phases. FSH, estradiol (E2),
and progesterone (P4) levels are also depicted across the
cycle (36 ).
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During the early years of the Reproductive Endocrine Unit, the
administration of a physiological regimen of GnRH through a portable
miniinfusion pump was demonstrated to induce normal puberty and
fertility in GnRH-deficient men and women (3, 4). Over the past decade,
the Unit has continued to refine the GnRH pump as a clinical and
research tool. Because the pump can be programmed to different settings
of GnRH dose and frequency, it is actively used as a probe of normal
hypothalamic-pituitary-gonadal physiology in both men and women (5, 6, 7).
Many patients with hypogonadotropic hypogonadism choose the pump for
formal fertility therapy. In men, the induction of spermatogenesis may
take months to years. However, in women, the development of a
preovulatory follicle is seen within 2 weeks of pulsatile GnRH
therapy.
After a baseline study demonstrated a complete absence of endogenous LH
pulsations in MO, administration of iv pulsatile GnRH was begun. As
documented by the Unit, the use of a closed system of prolonged iv
cannulation is safe in the setting of careful out-patient monitoring
(8). Similar to the vast majority of hypogonadotropic patients seen in
the Reproductive Endocrine Unit, MO had an excellent response to
pulsatile GnRH (9, 10). She recruited a single dominant follicle,
mounted her own endogenous LH surge, and conceived during that cycle,
leading to a healthy singleton pregnancy (Fig. 4
).

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Figure 4. Serum levels of LH, FSH, estradiol (E), and
progesterone (P) in patient MO with hypogonadotropic hypogonadism
undergoing exogenous pulsatile GnRH replacement. Patient MO received 75
ng/kg pulsatile GnRH, iv, and had a single dominant follicle seen on
ultrasound. Note the rising estradiol levels through her follicular
phase, the endogenous LH surge, and the rising progesterone levels
through the luteal phase. The positive serum hCGß symbol indicates
pregnancy.
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Similar to females, men with GnRH deficiency may qualify for pulsatile
GnRH therapy in the Units "pump program," if they demonstrate a
complete absence of LH pulsatility. Twenty to 25 men participate in the
program at any time, whether the clinical goals are virilization or
fertility. While undergoing prolonged therapy, men receive incremental
increases in GnRH dose until serum testosterone levels are in the
normal male range. When testicular volume reaches a certain threshold
size, ejaculates are examined for evidence of spermatogenesis (9).
By critically reviewing its 15-yr experience with hypogonadotropic
hypogonadism, the Reproductive Endocrine Unit has demonstrated that
approximately one third of patients have at least 1 other family member
with hypogonadotropic hypogonadism, anosmia, or delayed puberty (11).
Approximately 300 patients with GnRH deficiency (with or without
anosmia) have been entered into a relational database. Combined with
extensive family pedigrees and abundant biochemical data, this database
will facilitate the longitudinal follow-up of patients necessary for
sophisticated genetic studies. Although GnRH deficiency is a rare
disease, understanding the genes that cause this condition will add
fundamental insights into more common disorders of GnRH secretion,
including constitutional delay of puberty and hypothalamic
amenorrhea.
Follow-up. After delivering her first child, MO resumed
estrogen and progesterone replacement therapy. One year later, she
returned to the Reproductive Endocrine Associates for further ovulation
induction with the GnRH pump. She is now the mother of two healthy
daughters.
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Case II
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LB is a 31-yr-old woman who presented with secondary infertility
of 1-yr duration. Despite a lengthy history of oligomenorrhea, she
conceived spontaneously 3 yr earlier. Desiring a second child, but
having only one or two menses per yr, LB presented to another facility
for ovulation induction. She was referred to the Reproductive Endocrine
Associates when other providers were unable to obtain any follicular
response to high doses of recombinant FSH preparations.
The Reproductive Endocrine Associates is one of the few medical
practices in the country to perform ovulation induction. Approximately
10% of all new referrals are for either primary or secondary
infertility. A thorough history and examination are essential in the
infertility population so that patients can be directed to the
appropriate level of medical or surgical intervention. In LBs case,
such a review revealed that 3 yr earlier, she did not lactate
postpartum. This, coupled with her negligible response to recombinant
FSH as sole therapy, suggested that LB might have some degree of
pituitary insufficiency. More detailed endocrine testing revealed
secondary hypothyroidism in addition to her hypogonadotropic
hypogonadism; a magnetic resonance imaging scan demonstrated a paucity
of pituitary tissue. Because both LH and FSH appear to be required for
appropriate steroidogenesis during folliculogenesis (12, 13, 14), ovulation
induction was undertaken in the Reproductive Endocrine Associates using
human menopausal gonadotropin, a gonadotropin preparation containing
both LH and FSH.
Within the practice, multiple choices for ovulation induction are
available, including clomiphene citrate, exogenous gonadotropins, and
pulsatile GnRH. Despite the availability of newer recombinant
preparations, all gonadotropin formulations are associated with a high
rate of multiple gestation (as high as 2450% in hypogonadotropic
patients). In the Reproductive Endocrine Associates, gonadotropin
therapy is administered in a step-up protocol to determine the
threshold dose necessary for follicular development as originally
pioneered by Brown and colleagues (15). This approach is used for all
patients requiring exogenous gonadotropins for ovulation induction
regardless of the specific diagnosis (i.e. hypogonadotropic
hypogonadism, anovulation, idiopathic, etc.). An on-site
expert ultrasonographer provides the required continuity to patients
both within and between ovulation induction cycles. Within each cycle,
the size of each follicle is monitored in combination with same day
estrogen measurements, allowing subtle titration of gonadotropin doses.
The physicians relatively conservative dosing approach with exogenous
gonadotropins has yielded the lowest rate of multiple gestation in the
literature (14.8%) while maintaining pregnancy rates comparable to
those reported by other ovulation induction centers (10). There has
never been a case of clinical ovarian hyperstimulation, a potentially
life-threatening complication, within the ovulation induction
program.
Pulsatile GnRH, which maintains normal pituitary feedback mechanisms,
theoretically decreases the risk for multiple folliculogenesis and
multiple gestation. A head to head comparison of pulsatile GnRH
vs. exogenous gonadotropin therapy was conducted by the
Reproductive Endocrine Unit in 41 patients with hypogonadotropic
amenorrhea. Using life table analysis, the cumulative chance for
conception was higher with GnRH therapy (96%) compared with exogenous
gonadotropins (72%) (10). Although the risk of multiple gestation was
low in both groups and not significantly different, all higher order
multiple gestations (triplets) occurred in the gonadotropin-treated
group.
Multiple gestations have far-reaching consequences, not only
emotionally and financially to the couple, but to the health care
system as a whole. To draw attention to this important issue, members
of the Unit reviewed hospital charges for over 13,000 women undergoing
assisted-reproductive technologies at Brigham and Womens Hospital
over a 5-yr period (16). The predicted charges for a singleton delivery
were $9,845; for twins, $37,947; for triplets, $109,765. It was
estimated that this teaching hospital would have saved $3 million
dollars/yr if their multiple gestations due to assisted reproduction
had been singletons. The observations from this study have had a
far-reaching impact in the field of infertility; they continue to renew
the commitment of the Reproductive Endocrine Unit and the clinic
practice to improving the safety and efficacy of ovulation
induction.
If a patient fails to conceive using exogenous gonadotropins, she
is referred for in vitro fertilization (IVF). Uncovering
prognostic factors that may help to determine which patients are more
likely to have successful outcomes in IVF has been a challenge for many
investigative groups. Recent studies by the Reproductive Endocrine Unit
in collaboration with investigators at Brigham and Womens Hospital
have focused on the newly characterized gonadal proteins, inhibin A and
B, as predictors of outcome in assisted reproduction (17). Conclusions
from this work suggest that even in the prescreened population of
patients currently being accepted into IVF programs, the combination of
lower FSH and higher inhibin B levels is associated with a greater
chance for pregnancy.
Follow-up. Using a human menopausal gonadotropin
preparation (LH and FSH) at a dose of 150 U for 8 days, LB developed a
single dominant follicle with a peak serum estradiol level of 460
pg/mL. She then received hCG for ovulation, followed by intrauterine
insemination. A follow-up ultrasound at 6 weeks showed a single
gestational sac and fetal heartbeat.
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Case III
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MD is a 21-yr-old woman who presented with oligomenorrhea (fewer
than two menses per yr). Physical examination was notable for obesity;
extensive areas of acanthosis nigricans on the neck, back, axillae, and
between the breasts; and facial hirsutism.
PCOS is the most common endocrinopathy in premenopausal women. For
years, investigators, clinicians, and patients have struggled with the
terms polycystic ovary morphology, an ultrasound finding
that can be seen in up to 22% of normally cycling women, and
polycystic ovary syndrome, defined as chronic anovulation
and hyperandrogenism (18). Of women with a diagnosis of PCOS within the
practice, the most common presentations include oligomenorrhea (24%)
and hirsutism (22%) as well as acne, other menstrual irregularities,
infertility, scalp hair loss, and weight gain. Although PCOS is a
heterogeneous disorder, considerable attention has focused on the
insulin resistance seen in this syndrome, as suggested in MD by the
presence of acanthosis nigricans. Although PCOS-related insulin
resistance appears be a precursor of noninsulin-dependent diabetes
mellitus (NIDDM) (19, 20), patients with PCOS may also be at increased
risk for coronary artery disease (21, 22, 23) and dyslipidemia (24, 25).
Unlocking the pathophysiology of PCOS has been difficult. Several
investigators have noted a high prevalence of obesity in PCOS, and a
number of groups have described increased amplitude of LH secretion in
these women. Investigators in the Reproductive Endocrine Unit were the
first to demonstrate an increase in LH pulse frequency, suggesting
hypothalamic involvement in this disorder (26). Despite this growing
body of data, the relationship between body composition and
gonadotropin secretion had never been studied in detail. Unit
investigators have now examined gonadotropin abnormalities across a
spectrum of body weight in PCOS patients (27). Almost all patients
(92%), whether obese or lean, were shown to have an elevated LH to FSH
ratio. Moreover, LH correlated strongly in an inverse fashion with body
fat. That the relationship between LH and body fat is a continuously
distributed variable suggests that LH and obesity are strongly related
contributors to the PCOS phenotype. Thus, earlier views that lean and
obese PCOS patients represent distinct etiological subsets may not be
correct. PCOS may actually encompass one continuous diagnostic
spectrum, a concept that has implications for genetic studies of this
disorder.
The metabolic, reproductive, and cosmetic issues facing PCOS patients
create many clinical challenges. Management of oligomenorrhea is
usually accomplished through ovarian suppression with oral
contraceptive therapy. However, both the estrogen and progestin
components of oral contraceptives can exacerbate glucose intolerance
and hyperinsulinemia (28). Although obesity is common in PCOS, insulin
resistance is independent of body weight. Therefore, practitioners in
the Reproductive Endocrine Associates aggressively evaluate each PCOS
patient for abnormalities in glucose metabolism. Information garnered
from oral and iv glucose tolerance testing is being used to develop
simpler tests of insulin resistance for clinical practice.
Antihyperglycemic and insulin-sensitizing agents, such as metformin and
troglitazone, have been shown to reduce serum insulin
levels and androgens in some PCOS patients (29, 30).
Patients with PCOS often have very brisk responses to exogenous
gonadotropins, putting them at risk for ovarian hyperstimulation. The
Reproductive Endocrine Associates has had excellent success in
ovulation induction in PCOS patients using low dose gonadotropin
therapy without GnRH agonist down-regulation (31). Pulsatile GnRH is
also effective in approximately 60% of PCOS patients (32). Recent data
suggest that the role of antihyperglycemic agents in PCOS may extend
beyond hyperandrogenism to the management of oligomenorrhea and
infertility. Metformin has recently been shown to increase the
ovulatory response to clomiphene citrate in obese women with PCOS (33).
Although not FDA approved for the treatment of anovulatory infertility,
metformin may become one of a new family of fertility treatments for
this population.
Follow-up. Patient MD met diagnostic criteria for NIDDM,
making her one of a significant percentage of PCOS patients who exhibit
impaired glucose tolerance (31.1%) and NIDDM (7.5%) at a young age
(20). She was started on a formal weight reduction program, nutritional
counseling, and metformin therapy. Spontaneous monthly menses resumed
after 2 months of therapy, and her ovulatory status was confirmed with
luteal phase progesterone levels. Her glycemic control continues to
improve.
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Case IV
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BF is a 35-yr-old female with a history of metastatic gestational
trophoblastic disease treated with methotrexate, etoposide, and
actinomycin D. At the time of her original presentation, detection of
placental hCG to monitor remission and early recurrence of
trophoblastic tumors was difficult due to chemical homologies between
hCG and LH. An hCG assay based on two high affinity antipeptide
monoclonal antibodies (one directed against the carboxyl-terminal of
the ß-subunit of hCG and one directed against the
-subunit of
glycoprotein hormone) had recently been developed (34). Whereas
conventional assays demonstrated persistent levels of hCGß, the newer
immunoradiometric assay, with its greater sensitivity and specificity,
demonstrated that BF had indeed achieved clinical remission 6 months
after chemotherapy. Unfortunately, BFs laboratory studies
demonstrated a LH level of 87.2 IU/L and a FSH level of 64 IU/L,
consistent with hypergonadotropic hypogonadism. She presented to the
Reproductive Endocrine Unit to discuss her ovarian function and future
fertility.
By definition, premature ovarian failure (POF) is amenorrhea and an
elevated FSH level above the normal range in a woman under age 40 yr.
POF is one of the most devastating diagnoses for women in their
reproductive years. Some of the more common etiologies for this
condition include primary gonadal disorders (gonadal dysgenesis or
Turner syndrome), autoimmunity, and chemotherapy/radiation therapy. The
biochemical hallmark of ovarian failure (elevated FSH levels) and its
relationship to ovarian function have not always been clear. In
perimenopausal women, elevated FSH levels can be documented before the
cessation of menses. However, elevated FSH levels do not always mean
that fertility is not possible. A number of pregnancies have been
reported in women with POF, often during estradiol therapy.
Because of this latter observation, investigators within the
Reproductive Endocrine Unit explored whether estrogen therapy could
improve ovarian function in women with POF by performing a
randomized cross-over trial (35). Thirty-seven patients, including
patient BF, participated in this longitudinal study. Serial
observations via transvaginal ultrasound demonstrated high levels of
spontaneous folliculogenesis in these patients regardless of their
treatment assignment. Overall, approximately 80% of the women grew a
cyst greater than 10 mm, and close to half of the women ovulated. These
observations demonstrate that the elevated FSH levels used as the
biochemical hallmark of this condition occur much earlier than complete
follicular dysfunction. Although estrogen replacement therapy did not
improve fertility rates per se, it did not impede episodic
follicular development.
Follow-up. Patient BF underwent weekly blood sampling and
pelvic ultrasonography during the cross-over trial of estrogen
replacement. As she and her husband still desired fertility, BF used
the information on follicle development provided by the serial
ultrasound monitoring to coordinate the timing of intercourse. She
conceived during one of her monitored cycles and delivered a healthy
child approximately 3 yr after her last chemotherapy treatment.
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Collaborative research with industry: the Clinical Trials
Unit
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One of the newest additions to the clinical services provided by
the Reproductive Endocrine Associates is the Clinical Trials Unit. This
Unit has assembled the infrastructure to facilitate the transfer of new
drugs and technologies to patients as quickly as possible. The
Reproductive Endocrine Associates, with its extensive referral base,
has facilitated the recruitment of patients to a variety of clinical
trials. This Clinical Trials Unit works hand in hand with the
Reproductive Endocrine Units Reference Laboratory, allowing
industrial sponsors access to the broad normative database that has
been accrued in the Unit over the past 2 decades. The Reference
Laboratory has received national recognition for the development of
high quality reagents and innovative testing and provides rapid
turn-around time and electronic user-friendly interfaces for
accessioning and results reporting. The Unit is currently participating
in studies on the use of insulin-sensitizing agents in PCOS,
recombinant gonadotropins to induce spermatogenesis, and new GnRH
antagonists for various reproductive disorders in both men and
women.
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Commitment to training
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The Reproductive Endocrine Unit is an integral part of the
General Endocrine Fellowship Training Program of Massachusetts General
Hospital. Most endocrine programs include little or no formal training
in reproductive endocrinology. However, the Reproductive Endocrine Unit
and its clinical practice provide a strong tradition of excellence in
clinical and research training. For first year Fellows in
endocrinology, the Reproductive Endocrine Associates group practice is
the nucleus of that training commitment. Patient care sessions occur
daily, and every Fellow is partnered with one staff clinician in a
year-long clinical mentorship. Fellows see primarily new patients so
they can perform evaluations at the time of initial presentation. At
the conclusion of the Fellowship training, the patients are transferred
to the staff physicians rather than to new Fellows, so there is no loss
of physician continuity. Fellows perform dynamic pituitary and glucose
tolerance testing, observe ovarian ultrasounds, and participate in the
management of ovulation induction cases with the staff physician. They
may also participate in research admissions to the GCRC.
This commitment to training extends well beyond the fellowship years.
Over the past 2 decades, approximately 50 Fellows have been trained in
clinical and laboratory research within the Unit. The vast majority of
these trainees sustain active academic careers and have been successful
in garnering NIH or equivalent independent research support. The Unit
has established a mentorship program for women and minorities
particularly interested in pursuing academic careers in
reproduction.
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Educational commitment
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The Reproductive Endocrine Associates has a strong commitment to
education. Each year, staff members organize a weekly Clinical
Conference Series, addressing a broad spectrum of topics within
reproductive medicine. Speakers are invited from within the
Reproductive Endocrine Unit, the Pediatric Endocrine Unit, Gynecology,
Urology, Psychiatry, as well as from outside the institution. These
lectures provide a core curriculum in clinical reproductive
endocrinology for the first year Fellows. In the first 8 weeks, the
lectures cover practical management issues of common reproductive
problems. Over the ensuing 10 months, the speakers integrate clinical
and basic research principles and their clinical applications.
Approximately four sessions per yr are devoted to the presentation and
management of complex reproductive cases. The Unit also conducts a
weekly Journal Club. Articles may be chosen on any aspect of
reproductive biology, whether clinical or basic. Assembling individuals
from many different domains of research adds tremendous diversity to
the discussion and commentary of each journal selection.
The Reproductive Endocrine Unit also has established a yearly
curriculum for the Harvard-wide Reproductive Sciences Center Basic
Science Seminar Series. Speakers come almost exclusively from outside
MGH. Before the seminar, speakers spend a day within the Unit, visiting
individually with staff members and Fellows to discuss specific
research projects. Outside the Reproductive Endocrine Unit, the
clinical staff participate in teaching at a national level. Activities
of the staff include Clinical Symposia and "Meet the Professor"
sessions at the Annual Endocrine Society meeting, continuing education
courses sponsored by The Endocrine Society, and menopause symposia at
the American College of Physicians.
In summary, the Reproductive Endocrine Unit and its associated clinical
practice, the Reproductive Endocrine Associates, work synergistically
in a dual mission of clinical care and clinical investigation for
patients with reproductive disorders. This unique coupling occurs for
multiple reasons, including 1) the ability of the staff to recognize
that human conditions represent powerful physiological opportunities
for investigation; 2) the firm belief that continual communication
between clinical and basic research teams is required to improve
patient care; 3) the continued commitment of all faculty members to
make the most recent advances in therapy available to patients; and 4)
the generosity of patients who share their time and enthusiasm.
Received February 8, 1999.
Revised March 12, 1999.
Accepted March 18, 1999.
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