Transcript Preservation of Fertility - Philadelphia Trans

Preservation of Fertility for Pre- &
Post-Pubertal Trans People:
Current Reproductive Options &
Research In-Progress
A.M. Clark, PhD
Philadelphia Trans Health Conference 2012
Goal of this presentation
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Provide information about the current
and potential future options for trans
people to have genetically-related
(biological) offspring
(Will not be discussing adoption.)
Talking about trans people
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Descriptions of people in this
presentation will be based the
reproductive organs they have, except
in cases from the literature where
certain labels have been used.
Sources of Information
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Dr. Samuel Pang & Reproductive Science Center of
New England
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American Society of Reproductive Medicine (ASRM)
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Society for Assisted Reproductive Technologies (SART)
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International Society for Fertility Preservation (ISFP)
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Sperm Bank Directory.com
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American Association of Tissue Banks (AATB)
References
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De Sutter, P. 2007. Reproduction and fertility issues for transpeople. In:
Principals of Transgender Medicine and Surgery, R Ettner, S. Monstrey,
A.E. Eyler, eds, pp. 209-221
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De Sutter, P, 2009. Reproductive options for transpeople:
Recommendations for revision of WPATH’s Standards of Care, Intl J
Transgenderism 11: 183-185.
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Rainbow Health Ontario Fact Sheet: Reproductive Options for Trans
People (and references therein).
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Standards of Care for Health of Transsexual, Transgender, and Gender
Nonconforming People, WPATH, 7th Version (and references therein).
Reproductive Needs and
Rights of Trans People
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Health Care Needs of Transgendered Patients,
Lawrence et al., 1996, J Am Med Assoc 276:874
ASRM Ethics Committee Report (2009), “Access to
fertility treatment by gays, lesbians, and unmarried
persons.”
Assisted Human Reproductive Act in Canada (2004)
non-discrimination clause includes sexual orientation
and marital status.
Reproductive Needs and Rights
of Trans People The desire to have children and the
Reproductive wish in transsexual
men. Wierckx et al., 2012, Hum
Reprod 27:483-487
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Survey of 50 transsexual men
(Belgium)
64% had partners
54% wanted children
38% had considered freezing
oocytes
16% had children with female
partner inseminated with donor
sperm
6% had given birth to children
prior to medical transition
preservation of fertility in
transsexual women: A survey. De
Sutter et al., 2002, Intl J
Transgenderism 6(3)
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Survey of 121 transsexual
women in Western Europe
43% had partners
40% had biological children
77% answered that sperm
freezing should be offered to
all trans women prior to
hormonal treatment, but 45%
would have refused because of
the emotional link to their
“male” past
POST-PUBERTAL
ADULTS
PRESERVATION OF FERTILITY
Preservation of Fertility in
Adults
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Cryopreservation of sperm
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Method has been used since the 1950s
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Semen analysis should be performed prior to banking to determine
sperm quality and quantity
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Some sperm banks will perform initial freeze-thaw test
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Recommendation is to store samples from at least 3 ejaculates with
minimum of 2-days between ejaculates
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With poor sperm quality or quantity, current reproductive
technologies can still result in successful pregnancy
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Sperm can be frozen indefinitely – successful pregnancies known
from sperm frozen for more than 10 years
Preservation of Fertility in
Adults
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Cryopreservation of sperm
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Verify bank has accreditation from American Association of Tissue
Banks
Semen sample can be collected at clinic or at home – some sperm
banks require sample collection on-site
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Sample collection methods
 Masturbation (most common)
 Special (nontoxic) condom via intercourse
 Electroejaculation
 Minor surgery to remove sperm from epididymis or testis
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No known detrimental effects of freezing on sperm DNA
Preservation of Fertility in
Adults
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Cryopreservation of oocytes (eggs)
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Method not systematically used until the 1990s
Initially, outcomes were poor – now >900 live
births recorded from frozen oocytes with no
apparent increase in abnormalities
Still considered “experimental” by ASRM but
expected to be a more “standard” method in the
near future
Preservation of Fertility in
Adults
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Cryopreservation of oocytes (eggs)
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Egg bank clinics may first evaluate ovarian reserves by
ultrasound and check blood hormone levels
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Ovarian stimulation & egg retrieval
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May begin with GnRH analogue to suppress endogenous
pituitary hormones
Self-injection of (pituitary) hormones to stimulate ovarian follicles
to develop ~12 days, possibly with ultrasound monitoring every
3-4 days
Retrieval under anesthesia using vaginal ultrasound-guided
needle aspiration of oocytes from ovarian follicles
Preservation of Fertility in
Adults
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Cryopreservation of oocytes (eggs)
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Two methods with goal of avoiding formation of
ice crystals either within the oocytes or in the
surrounding liquid
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Controlled-rate freezing
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Oocyte is dehydrated in cryoprotectants and temperature is
reduced slowly at a controlled rate
Vitrification
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High concentration of cryoprotectants + ultra-rapid freezing
rate, forming a glass-like (vitrified) state
Preservation of Fertility in
Adults
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Cryopreservation of oocytes (eggs)
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Potential risks of ovarian stimulation
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Ovarian cysts – may cause pelvic pain
Mild/moderate ovarian enlargement with possible
abdominal distention/pain in ~20% of patients
Ovarian hyperstimulation syndrome (OHSS)
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Risk can be up to 6% depending on doses of hormones
Ovaries enlarge and leak fluid into abdomen
Possible pleural effusion, blood clots, abnormal kidney
function
Can be life-threatening and may require hospitalization
Preservation of Fertility in
Adults
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Cryopreservation of embryos
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Better success rates than with cryopreservation
of oocytes
For individuals with ovaries, “Embryo freezing is
the most efficient technique for fertility
preservation.” (ISFP)
Considerations:
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Requires ovarian stimulation and retrieval of oocytes
Individual might not have sperm donor/partner at time
of fertility preservation
Preservation of Fertility in
Adults
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Because hormone therapy inhibits folliculogenesis and
spermatogenesis, the desire to procreate after medical
transition would require individuals to stop hormone therapy
for months or even years in order to produce germ cells
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Spermatogenic cycle = 74 days + ~15 days maturation in the epididymis
Development of a primordial follicle to a preovulatory dominant follicle =
almost one year (although secondary and tertiary follicles might be present
and reinitiate development once hormone therapy is stopped)
Hormones would render ovaries unresponsive to stimulation for oocyte
retrieval
Recovery of gamete development might not occur depending on the age of
the individual and the length of time they have been on hormone therapy
Preservation of Fertility in
Adults
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Questions:
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How long can sperm be retrieved from individuals once they have
started hormones?
Are some sperm produced in testes of individuals who have been on
hormone therapy mid-to-long term?
(My) Answer: The risk of epigenetic effects from
hormone treatment that could potentially be passed
onto offspring should not be ignored
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Clear sperm-related effects for nutrition, alcohol consumption, toxins
smoking, drug use
Reviewed in: Epigenetics and the origins of paternal effects. Curley
et al., Hormones and Behavior 2011 59:306-314
Preservation of Fertility in
Adults
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Cryopreservation of gametes (sperm and oocytes)
should be performed before individuals begin
transition-related hormone therapy
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However, this may not be possible due to cost, lack
of information/counseling, unacceptable potential
delay of transition, unacceptable link to “genderbased” function, unacceptable clinical procedures
(e.g. ovarian stimulation and egg retrieval)
Preservation of Fertility in
Adults - Future
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Cryopreservation of ovarian or testicular
fragments
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Currently experimental
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Would avoid difficulties of cryopreservation of
oocytes, sperm or embryos
Preservation of Fertility in
Adults - Future
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Cryopreservation of ovarian or testicular fragments
June 28, 2005
Preservation of Fertility in
Adults - Future
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Cryopreservation of ovarian or testicular fragments
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The female-to-male transsexual patient: a source of human ovarian
cortical tissue for experimental use. Van Den Broecke et al., 2001
Hum Reprod 16:145-147
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Ovarian tissue donated by 21-year-old FTM treated with testosterone undecanoate
for 12 months
2mm x 1mm ovarian cortex frozen-thawed fragments transplanted subcutaneously
into 17 female immunocompromised mice (3 fragments/mouse)
10-weeks post-grafting, mice injected with FSH for 14-days
86% of grafts recovered, all ~50% reduced in size
Non-grafted ovarian biopsy = 98.6% primordial and 1.4% primary follicles
Engrafted ovarian fragments = 79.4% primordial and 20.6% later staged follicles,
including 2.1% secondary and 1.4% pre-antral follicles
POST-PUBERTAL
ADULTS
REPRODUCTIVE OPTIONS
Reproductive Options for
Adults
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Needs influenced by availability of
gametes (sperm, eggs) from both
members of a couple and whether one
member of the couple will carry the child
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Sperm/egg donors – known or anonymous,
may involve sperm/egg bank and/or egg
donor agency
Gestational carrier / surrogate – often
involves surrogacy agency
Reproductive Options for
Adults
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One member of the couple has ovaries (oocytes) and
uterus, will be inseminated and will carry the child
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Example: Fenway Health Clinic, Boston
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Couple attends orientation at the clinic
Couple charts menstrual cycles for 3 months by monitoring basal body
temperature (BBT), note changes in cervical mucus and cervix and
practice using ovulation prediction kit
Enrollment Visit for reviewing BBT charts, lab results
Preconception Counseling Visit for discussing current state of health and
medical history, information discussion, mandatory medical tests
Clearance for procedure based on medical assessment and medical test
results
Order sperm from bank if necessary
Sperm deposition timed with ovulation -- intra-vaginal (can be done at
home using a kit), intra-cervical or by intrauterine insemination (IUI)
Reproductive Options for
Adults
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Intrauterine Insemination (IUI)
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Improves contraception rates, especially in cases where
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Sperm cells first washed and concentrated
Sperm cells then placed directly into uterus
Individual has ovulatory disorder that responds to co-administered fertility
medication
Individual has mild endometriosis, does not ovulate, has structural
problem of the uterus or oviduct
Sperm quality and/or concentration is low
Some (low) risks: infection, uterine cramping, side effects and/or
multiple pregnancy if fertility medications are administered, STI from
sperm
Reproductive Options for
Adults
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In Vitro Fertilization (IVF) / Assisted
Reproductive Technologies (ART) may
be employed when:
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Cryopreserved eggs are used
Donated eggs are used
Sperm cells are poor quality and/or incapable
of fertilizing the egg (can use Intracytoplasmic
Sperm Injection – ICSI)
Individual with ovaries who will carry the child
has fertility issues or structural problems of
the reproductive tract
A gestational surrogate will carry the child
Reproductive Options for
Adults
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In Vitro Fertilization (IVF) / Assisted Reproductive
Technologies (ART)
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The cycle preceding ART:
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Oral contraceptives may be used to synchronize irregular cycles
and help prevent ovarian cysts from GnRH analog
GnRH analog may be administered to suppress endogenous
pituitary hormones
Baseline pelvic ultrasound –checks for ovarian cysts
ART Cycle: Same steps as given for ovarian stimulation
and egg retrieval for oocyte cryopreservation
Reproductive Options for
Adults
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In Vitro Fertilization (IVF) / Assisted Reproductive
Technologies (ART)
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Sperm is collected fresh if frozen sperm are not being
used, is washed to remove semen
Sperm and eggs are cultured together under special
conditions for fertilization - or - ICSI is performed
Reproductive Options for
Adults
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In Vitro Fertilization (IVF) / Assisted
Reproductive Technologies (ART)
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Fertilized eggs/embryos allowed to develop “in
the dish”
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Embryos may develop at different rates
Can help distinguish which are “good” embryos
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Next day (Day 1): Single cell with 2 nuclei
Day 2: 4-cell embryo
Day 3: 8-cell embryo
Day 5: blastocyst (>80 cells, fluid-filled cavity, inner cell mass)
Reproductive Options for
Adults
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In Vitro Fertilization (IVF) / Assisted
Reproductive Technologies (ART)
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Embryo transfer:
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Best embryos selected for transfer based on recipient’s
age, appearance of embryos
Embryos placed in recipient’s uterus
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Menstrual cycle of gestational surrogate, if used, must be
synchronized to accept embryo(s) at the proper time so
uterine lining can support implantation
If fresh eggs from an egg donor are used, the cycles of both
the egg donor and the embryo recipient must be synchronized
Reproductive Options for
Adults
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In Vitro Fertilization (IVF) / Assisted Reproductive
Technologies (ART)
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Also with embryo transfer:
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Some clinics will perform assisted hatching
Hormonal support for uterine lining – progesterone
supplementation by vaginal, oral and/or injectable route, usually
administered the day of or after oocyte retrieval
Progesterone support administered daily until pregnancy test
Pregnancy test performed 9-12 days after embryo transfer and
repeated 2-days later if positive
Close evaluation of pregnancy to identify miscarriages or ectopic
pregnancies and counsel for multiple pregnancy
Patient released to obstetrician 8-10 weeks of gestation
Reproductive Options for
Adults
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Gamete Intrafallopian Transfer (GIFT) / Assisted
Reproductive Technologies (ART)
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Unfertilized sperm and eggs are placed together in the
fallopian tubes where fertilization takes place
May be used in place of IVF by individuals with less
severe infertility issues
Does not result in issue of unused, stored frozen embryos
Requires laparoscopy under general anesthesia
Could result in multiple pregnancy
Rarely performed - Only ART not excluded by the Catholic
church
Reproductive Options for
Adults
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Breastfeeding/lactation
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For individuals whose breast development was a result of transition
hormone treatments, lactation may be stimulated with methods used
by mothers who adopt, although no data available for trans people
using this method
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Wittig & Spatz, 2008 Am J Maternal Child Nursing 33:76
For individuals who have had chest masculinization surgery and who
gestate and give birth, remaining breast tissue may grow with
pregnancy and might even lactate and/or become inflamed (mastitis)
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Might require revision post-pregnancy, as tissue may not completely
regress
Drugs are available to stop lactation
POST-PUBERTAL
ADULTS
COSTS AND LEGAL
CONSIDERATIONS
Reproductive Options for
Adults – Costs of Procedures
“Costs of different
procedures vary from
clinic to clinic and
from state to state,
with costs at RSC
New England being
on the low side of the
range. Costs of
surrogacy also vary
and could be up to
twice the amount
given here.”
www.GayIVF.com
www.RSCNewEngland.com
Reproductive Options for
Adults – Costs of Procedures
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IUI (Intrauterine Insemination)
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IVF (In Vitro Ferilization)
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~$15,000 per treatment cycle, including meds
Egg donor
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$300-$500/attempt (cycle), $300 ultrasound, $100-$1000 fertility
drugs, $1000/cycle donor sperm
$10,000 - $15,000 – covers compensation to egg donor, agency and
legal fees, donor expenses (such as travel, etc.)
Surrogate
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$40,000 - $60,000 – covers compensation to surrogate, agency and
legal fees, surrogate expenses
Reproductive Options for
Adults – Legal Considerations
“I am not a lawyer so
cannot provide legal
counsel. These are
simply issues which I
raise to heighten the
awareness of the
audience that they
need to have legal
counsel with an
attorney who is
familiar with this
highly specialized
area of law.”
www.GayIVF.com
www.RSCNewEngland.com
Reproductive Options for
Adults – Legal Considerations
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Donors: sperm and eggs
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Prenatal & perinatal care
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Known donor – need to agree on involvement, parental and visitation
rights, etc.; need to document expectations of both parties in a legal
contract
Anonymous donor – laws vary from state to state regarding
anonymity, disclosure, etc.
Laws vary from state to state whether the (non-pregnant) partner (if
not married) can participate in prenatal visits and birth.
Living wills are needed to determine fate of frozen embryos if one
partner becomes incapacitated
Second parent adoption
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May be necessary if intended parents are not married to each other –
affects custody, hospital visitation, travel, taxes, etc.
Reproductive Options for
Adults – Legal Considerations
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Surrogacy
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Banned in several states (e.g. New York)
Need to ensure that surrogate lives in and delivers baby in a state
that is “surrogacy-friendly” or court may rule in favor of surrogate if
she wants to keep the baby.
Massachusetts is one of the most surrogacy-friendly states – having
a “pre-birth order” from the court allows the names of the intended
parents to go directly on the birth certificate at the time of birth.
Otherwise, the surrogate needs to “give the baby up for adoption” and
the intended parents need to “adopt” their own baby, which adds the
complications of adoption laws.
Reproductive Options for
Adults – Legal Considerations
www.GLAD.org
Reproductive Options for
Adults – Legal Considerations
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www.GLAD.org
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Chapter 3: Relationship
Recognition and
Protections
Chapter 4: Protecting
Parental Rights
Chapter 6: Parental
Rights After Relationship
Dissolution
PRE-PUBERTAL
CHILDREN
PRESERVATION OF FERTILITY
EXPERIMENTAL METHODS
Preservation of Fertility in Children
Experimental Techniques
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Children on hormone blockers will not go
through puberty. Will not have mature gametes
to preserve.
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Teenage trans children with ovaries might
respond to ovarian stimulation for collection and
cryopreservation of eggs, even if they have
been on hormone blockers. May need to go off
the blockers for several months – “uncharted
territory.”
Preservation of Fertility in Children
Experimental Techniques
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An ethical consideration
Children are not necessarily thinking about
having their own children, so parents may end
up making decisions to preserve their children’s
reproductive cells or tissues that their children
will then have control of when they become
adults.
Preservation of Fertility in Children
Experimental Techniques
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Methods are currently being developed for children and
adults who have cancer and who will be rendered sterile by
chemotherapy and radiation treatments.
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International Society for Fertility Preservation (ISFP)
Preservation of Fertility in Children
Experimental Techniques
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Cryopreservation of ovarian tissue (pieces)
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Children have abundant follicles throughout the ovarian cortex
Puberty blockers would keep follicles in primordial stage
Ovaries could be removed upon medical transition, sectioned into
small pieces and slow-frozen in cryoprotectant
Pieces could be stored until needed for generating embryos
Would require culture and in vitro maturation of follicles/oocytes and
possibly ICSI to generate embryos
Live young (mice, kittens) have been born from this
procedure
Studies published where human follicles were matured in
vitro
Preservation of Fertility in Children
Experimental Techniques
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Cryopreservation of sperm
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Sperm have been successfully collected from
children as young as 11 years of age
Number of sperm low, so may require two or three
ejaculates
Would need to be done prior to use of puberty
blockers
May be difficult for children who are uncomfortable
with their birth sex
Sperm may not be mature for fertilization, so may
require ICSI
Preservation of Fertility in Children
Experimental Techniques
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Cryopreservation of testicular tissue
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Puberty blockers would stop development of spermatogonia
Testes could be removed upon medical transition, sectioned into small
pieces or dissociated into cell suspensions and slow-frozen in
cryoprotectant
Pieces/suspensions could be stored until needed for generating sperm
Would require culture and in vitro expansion and maturation of
spermatogonia to spermatid stage
Up to 60% post-thaw viability reported with human testicular
cell suspensions.
Some development of germ cells in cultured human
testicular tissue and cell suspentions.
Recent development of mouse sperm from testis cell
suspensions in a 3-D soft agar culture system
WHAT WILL THE MORE
DISTANT FUTURE HOLD?
Recent Headlines
January 18, 2012
QUESTIONS?