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THIRD PARTY REPRODUCTION
&
CURRENT CONCEPTS IN ART
DR. VANDANA BANSAL
MS, D.PHIL.(GOLD MEDALIST), DGO, FCGP
Senior Gynaecologist & Obstetrician
Infertility & IVF Specialist
Director
Vandana Women’s Hospital
Arpit Test Tube Baby Centre
Jeevan Jyoti Hospital
Introduction
ī‚—The process of reproduction has long fascinated
man kind particularly from scientific perspectives.
ī‚—The sole objective of any living organism is to
procreate i.e. to reproduce itself.
ī‚—With an average monthly fecundity rate of 20%,
human beings are not fertile mammals.
ī‚—10-15% of couples has difficulties in conceiving and
seeks special fertility care at least once during their
reproductive life time.
Infertility
Infertility is defined as a failure to conceive within one year of
regular unprotected coitus
– Primary Infertility – patient’s who have never conceived
– Secondary Infertility – indicates previous pregnancy
but
failure to conceive subsequently’.
80% of couple conceive within 1st
year
10% conceive by the end of 2nd
year
10% remain infertile by end of 2nd
year
Incidence - 10% to 15%
Infertility
Prevalence and Overview of Treatments
ī‚—The overall incidence of infertility
has remained relatively unchanged
for the past 30 years (Speroff & Fritz, 2005).
ī‚—Approximately half of all women
who
receive fertility care achieve
conception
leading to a live birth (Speroff & Fritz, 2005).
Causes of Infertility
Female factor
Ovulatory dysfunction
Cervical factors
Tubal factors
Endometriosis
Uterine factors – Fibroid uterus,
Uterine
Synechiae, Congenital
malformation of uterus
Vaginal factors – Vaginal Atresia,
Septate vagina
Immunological
Coital problem
Hormonal
Unexplained
Male factor
Defective spermatogenesis
Abnormal Semen Parameters
Obstruction of the duct
Failure to deposit sperm high
in the vagina
Idiopathic
Varicocele
Hormonal
Systemic causes
Immunological
Origin of Reproduction
So, God created man in His own image, in
the image of God created He him; male and
female created. And God blessed them and
God said unto them. Be fruitful and
multiply and replenish the earth and
Subdue it.
(Genesis 1:27-28)
Treatment Optionsâ€Ļ Overcoming Infertility
Nearly 90% of all infertility cases, both male
and female factor, can be successfully treated.
Treatment options are:
īƒ˜ Ovulation Induction
īƒ˜ Medical & Surgical treatment of Male
īƒ˜ Laparoscopic & Hysteroscopic Surgery for Female
īƒ˜ Intrauterine Insemination (IUI)
īƒ˜ Assisted Reproductive Technology (ART)
īƒ˜ Third party Reproduction
Human Reproduction – Changed
ī‚—25th
July, 1978
ī‚—Louise Joy Brown
ī‚—World’s First Successful Test Tube Baby
Landmark Event in Reproductive Revolution
Science Proves Wonders
Third Party Reproduction
ī‚—Third party reproduction refers to the use of
oocytes, sperm, embryos, or uterus that has
been provided by a third person (donor) to
enable an infertile individual or couple (intended
parent) to become parents.
ī‚—Ethical, moral, religious and legal concerns play a
significant role in these treatments
ī‚—They have allowed the miracle of childbirth to those
who might otherwise be unable to achieve this goal.
With increasing age, the woman’s ovaries
run out of eggs(limited ovarian reserve)
The only option these women have for having a baby is IVF egg donation â€Ļthird party
There is also an increasing incidence of
Premature Ovarian Failure & Diminished Ovarian
Reserve
ī‚—For these women to concieve the only way out is
to use donor eggs(third party)
ī‚—Aged women
ī‚—Oophrectomy cases
ī‚—Cancer ovary and operated or irradiated
ī‚—Premature ovarian failure(premature
menopause)
There is an increasing incidence of non
obstructive azospermia
The only chance these couple have to have a
baby is through sperm donationâ€Ļâ€Ļthird party
Some women have untreatable uterine
abnormality RKH, endometrial TB,
hystrectomy, etc
The only chance of these couples to
have babies is through â€Ļâ€Ļ..â€Ļâ€Ļ
â€Ļâ€Ļâ€Ļâ€Ļâ€Ļthird party reproduction
Indications for Third-party reproduction
Women without functional ovaries
ī‚—Advanced maternal age
ī‚—Surgical or natural menopause
ī‚—Premature ovarian failure
ī‚—Previous chemotherapy or radiotherapy
ī‚—Women born without functional ovaries
Women with functional ovaries
ī‚—Recurrent pregnancy loss
ī‚—Repetitive IVF failures/poor response
ī‚—Women without functioning uterus
ī‚—Uterus that is unsuitable for pregnancy such as extensive fibroids,
adenomyosis, or Asherman’s
ī‚—Women with a serious medical condition that increases significant
morbidity, or even mortality if pregnancy occurs
ī‚—Inheritable disorders
Male & Female same sex couple
Types of Third Party Reproduction
īļOocyte donation
īļSperm Donation
īļEmbryo Donation
īļSurrogacy
īļ Traditional surrogacy
īļ Gestational surrogacy
What is Oocyte Donation?
ī‚— Egg donation is the part of third party reproduction.Egg donation is the part of third party reproduction.
ī‚— Eggs are retrieved from a young woman ( < 33 yrs ) calledEggs are retrieved from a young woman ( < 33 yrs ) called
the donor.the donor.
ī‚— These eggs are fertilized with the sperms of the recipient’sThese eggs are fertilized with the sperms of the recipient’s
husband.husband.
ī‚— Resultant embryo is transferred to the uterus of theResultant embryo is transferred to the uterus of the
recipient.recipient.
Oocyte Donation
ī‚—Oocyte donation has been used for more than 20 years to help
infertile couples become pregnant through IVF
ī‚—The first pregnancy achieved with egg donation was
reported in 1984.
ī‚—Oocyte from a donor are fertilized with male partner’s sperm
& resulting embryos are transferred into the female partner’s
uterus
Oocyte Donation: Indications
Women without ovarian function:
ī‚— Advanced maternal age
ī‚— Surgical or natural menopause
ī‚— Premature ovarian failure
ī‚— Women born without functional ovaries
ī‚— Previous chemotherapy or radiotherapy
Women with ovarian function:
ī‚— Recurrent pregnancy loss
ī‚— Repetitive IVF failures/poor response
ī‚— Inheritable disorders
Male same sex couple
The Oocyte Donation Process
The recipient couple
ī‚—Psychological issues
ī‚—Medical Screening
ī‚—Legal Issues
ī‚—Ethical concerns
The donor
ī‚—Donor recruitment
ī‚—Donor Screening
ī‚—Donor matching
Psychological consultation for
oocyte donor recipients
ī‚—The decision to proceed with donated oocytes is
complex, and patients and their partners (if
applicable) may benefit from psychological
counseling
ī‚—clinician should strongly recommend psychological
counseling by a qualified mental health professional
ī‚—The assessment should include a clinical interview
and, where appropriate, psychological testing.
ī‚—In cases of directed donation, the potential impact of
the relationship between the donor and recipient
should be explored
Evaluation of the oocyte recipient
A. Medical and reproductive history
B. A complete general physical examination
including a pelvic examination.
C. Assessment of the uterine cavity (HSG, saline
infusion ultrasonography)
D. Standard preconceptional testing and
counseling
a. Blood type, Rh factor, and antibody screen.
b. Rubella and varicella titers.
c. HIV, syphilis, Hepatitis, Neisseria gonorrhoeae and
Chlamydia trachomatis
Evaluation of the partner of the
oocyte recipient
1. Semen analysis for male partners.
2. Blood type and Rh factor.
3. Serologic test for syphilis.
4. Hepatitis B surface antigen.
5. Hepatitis B core antibody (IgG and IgM).
6. Hepatitis C antibody and NAT.
7. HIV-1 (AB and NAT), HIV-2 AB testing
8. Appropriate genetic screening and testing
based on history
Classification of Donors
Oocyte donors can be classified based on the
anonymity of their identity.
ī‚—Anonymous Donors:
ī‚Ą Recruited and screened by the ART program or by a private
agency.
ī‚—Directed donors:
ī‚Ą Generally recruited by the recipients, and screened by
agencies or centers
ī‚Ą The donor is generally a close relative or friend
ī‚—IVF programs:
ī‚Ą Women undergoing IVF may agree to donate their
excess eggs to infertile patients
Donors
ī‚—IVF patients, willing to share their extra- oocytes
(OOCYTE SHARING PROGRAMME( COMMON )
ī‚—Women with tubectomy, willing to be hyperstimulated
( MONETARY COMPENSATION)
ī‚—Known donors include family members who come
forward to donate their oocytes ( FAMILY )
ī‚—Professional donors, recruited after advertisement
(MONETARY COMPENSATION)
ī‚—Volunteers , philanthropic enough to donate their oocytes
(RARE BUT MAY FIND SUCH)
Selection of Donors
ī‚— Oocyte donation may be undertaken with known or anonymous
ī‚— Psychological evaluation and counseling
ī‚— Oocyte donors should be of legal age (21 - 34 years).
ī‚— Donors less than 21 years of age should have psychological evaluation
and decision should be on an individual basis.
ī‚— If a donor is over 34 yr, it should be revealed to recipient concerning
cytogenetic risks and pregnancy rates.
ī‚— Proven fertility in the donor is desirable
ī‚— The donor should undergo appropriate genetic evaluation
ī‚— If sharing of oocytes is contemplated, informed consent must be
obtained
Donor Screening
ī‚—Suggested medical ,personal, family (genetic) &
reproductive history
ī‚—Complete blood count with platelets
ī‚—Blood type
ī‚—Hepatitis screen
ī‚—VDRL
ī‚—HIV-1, HIV- 2
ī‚—Cervical cultures for gonorrhoea and Chlamydia
ī‚—Pap smear
ī‚—Transvaginal ultrasound of pelvis
ī‚—Appropriate genetic tests
Proper selection of donor thorough evaluation & treatmentProper selection of donor thorough evaluation & treatment
of recipient. Optimum dose of Gonadotrophins and properof recipient. Optimum dose of Gonadotrophins and proper
monitoring of donor avoid complications in egg donor.monitoring of donor avoid complications in egg donor.
Matching the Intended Parent to
an Oocyte Donor
ī‚—Donors are matched as closely as possible with the
recipient couple for characteristics, such as hair color,
eye color, ancestry; occupation, educational level;
previous donation history
ī‚—Medical matching (Blood group & other diseases)
ī‚—Compensated for their time & effort
ī‚— Compensation remains the same no matter how many
oocytes are retrieved
Algorithm of Oocyte Donation
Recipient evaluation(USG to monitor development of oocytes, blood tests to check E2 levels).
↓
Donor Recruitment
↓
Donor Screening
↓
Obtaining informed consent from recipient and donor
↓
Synchronization of donor and recipient cycles
↓
Prescription of hormones for the recipient
↓
Ovarian stimulation of donor
↓
Oocytes retrieval from donors
↓
Fertilization of oocytes
↓
Embryo Transfer
↓
Maintenance of pregnancy in recipient
Donor Treatment Cycle
Synchronisation
ī‚—The synchronization of cycles in the donor
and recipient is extremely important to the
success of the oocyte donation.
ī‚—The treatment cycles of the oocyte donor
and the cycling recipients involve pituitary
suppression by GnRH agonist
ī‚—Alternative protocols using GnRH
antagonist can also be used.
Egg Donation Treatment Sequence
Actual treatment is individualized
Schematic Diagram of an Oocyte Donor
Stimulation Protocol
Alternative protocols using GnRH antagonist can also be used
Ovum Pick Up
ī‚—Approximately 36 hours after the
hCG injection
ī‚—Short G/A anesthesia
ī‚—TVS aspiration is done with needle
connected to aspiration pump
ī‚—Identification of oocytes is done in Lab
simultaneously
ī‚—Earlier laparoscopic aspiration was done
ī‚—Antibiotic cover is given for 5 days
ī‚—Patient can go home after 3-4 hours
Protocol for Recipient
ī‚—The uterus is prepared using hormones (estrogen and
progesterone) to mimic the natural menstrual cycle
ī‚— GnRHa is used to suppress the pituitary gland to prevent the
patient from ovulating during the preparation of the uterus
ī‚—Once the pituitary gland is suppressed, exogenous estrogen is
given & in turn it thickens the uterine lining
ī‚— Pills, Patches, or even Injections
ī‚—Progesterone started once endometrium is >8mm & on the
day of oocyte retrieval in donor
ī‚— Vaginal suppository or Gel or as Injections
ī‚—The no. of days progesterone is given before the transfer must
match the stage of embryo development
Schematic Diagram of a Recipient Protocol.
â€ĸIf the pregnancy test is positive, recipients are asked to continue the
estrogen and progesterone replacement until 10 weeks of gestation.
â€ĸIf the pregnancy test is negative, patient can stop the hormonal
replacement. E – estrogen; P –progesterone.
Endometrial Receptivity
īļ Endometrial receptivity is the window of time when the uterine
environment is conductive to embryo acceptance and subsequent
implantation
īļ Timely expression of a number of complex molecules like hormones,
cytokines & growth factors, and their crosstalk play a crucial role in
preparing receptive endometrium
īļ Endometrial histology is influenced by estradiol & progesterone and
their synchronization is essential for implantation window
īļ Parameters for assessing endometrial receptivity include:
īƒ˜ endometrial thickness (>7 - <14 mm)
īƒ˜ endometrial pattern (triple-line pattern)
īƒ˜ endometrial and subendometrial blood flow (within Zone 3 )
Window of Receptivity
ī‚—The condition of uterus becomes optimal for implantation for
a brief period during leuteal phase known as Window of
receptivity
ī‚—Short - last for 4 days (Day 20-24 of the menstrual cycle)
ī‚Ą +6 to 10 (Bergh and Navot 1992)
ī‚Ą +3.5 (Rogers 1989)
ī‚Ą +5 to 7 (Psychoyochos 1993)
ī‚—During this period endometrium undergoes important
changes that makes it receptive to the implanting embryo
ī‚—Key factor in implantation is the synchrony between embryo
development & endometrial receptivity
Post ovulatory
Days
WINDOW OF RECEPTIVITY
(Implantation Window)
JARVELA et al 2005;
Luteal Phase Support
īļ Vaginal progestin Pressaries
īļ 100 BD- if CC/FSH/HMG cycle
īļ 200 TDS- if GnRHa+HMG/FSH
īļ Oral – Dehydrogestone 10 mg BD
īļ HCG 2000-2500 IU IM day 3
īļ Progesterone – 50-100 mg IM
Rationale and Indications
â€ĸ COH results in abnormal endometrial Development
â€ĸ High level of estrogen seen in COH may cause premature luteolysis
â€ĸ Pituitary down regulation with GnRHa is detrimental to luteal phase
â€ĸ Ovarian aspiration disrupts granulosa cells
â€ĸ Important to synchronise embryo and endometrium for successful
implantation
Concerns & Complications
â€ĸ Ethical, legal, religious & social issues
â€ĸ Relationship between biological & social parents, &
safeguarding of the interests of the off spring, may be resolved
by specific legislation pertaining to each country
â€ĸ Adequate study of the health risks of oocyte extraction,
including long-term risks
â€ĸ Medical costs for adverse effects caused by the procedure
â€ĸ True informed consent from women who provide oocytes
â€ĸ Exploitation of poor women
â€ĸ No meaningful oversight
Pregnancy Rates with Egg
Donation
Depends on:
ī‚—Age of the Donor & Recipient
ī‚—Cause of the couple's infertility
ī‚—Quality & Developmental stage and number of embryos
transferred
ī‚—Average live-birth rate per fresh embryo transfer is
55.1% (CDC , 2009)
ī‚—The major risk for egg-donor programs is multiple
gestations- 39.9% (CDC, 2009)
Legal Issues
ī‚—Egg donation raises questions regarding all four of
the basic principles of medical ethics: autonomy,
justice, beneficence, and non-maleficence.
ī‚—Infertility specialists must consider these conflicts of
interest.
ī‚—Egg donation is regulated and / or prohibited in many
countries.
ī‚—The egg recipient and the father of the child are the legal
parents.
ī‚—Most egg donors express a strong desire not to be
identified by the children.
ī‚—Should donor identity be revealed to egg donation child
once he/she reaches the age of 18 years??
Sperm Donation
SPERM BANKS
Sperm Donation
ī‚— Artificial insemination using donor sperm has been practiced for
over a century.
ī‚— The first published reports about the practice were in 1945.
ī‚— Over the past 10 years, the utilization of donor sperm has decreased
due to use of ICSI
ī‚— Since the late 1980s, with the emergence of AIDS artificial donor
insemination has been performed exclusively with frozen and
quarantined sperm.
ī‚— Current FDA and ASRM guidelines recommend that sperm be
quarantined for at least six months before being released for use
ī‚— Therapeutic donor insemination (TDI) may be used to achieve
pregnancy where appropriate indications exist.
Indications for Sperm Donation
Therapeutic donor insemination (DI or TDI) is
appropriate in
ī‚— Severe abnormalities in the semen Parameters
ī‚— Azoospermia : congenital or acquired.
ī‚Ą Obstructive azoospermia
ī‚Ą Non-obstructive azoospermia
ī‚— Severe oligospermia
ī‚— Seminal fluid abnormalities
ī‚— Single woman desiring pregnancy
ī‚— Lesbians
ī‚— DI is also indicated if the
ī‚Ą male has ejaculatory dysfunction
ī‚Ą male has significant genetic defect
ī‚Ą female is Rh-sensitized and the male partner is Rh-positive.
Psychological Consultation for
Recipients
ī‚—The decision to proceed with donor
insemination is complex , may benefit
from psychological counseling
ī‚—The clinician should strongly recommend
psychological counseling by a qualified
mental health professional
ī‚—In cases of directed donation, the
potential impact of the relationship
between the donor and recipient should
be explored
Evaluation of the Female Recipient
A. Medical and reproductive history
B. A complete general physical examination including a
pelvic examination.
C. Assessment of the uterine cavity (HSG, saline infusion
ultrasonography)
D. Standard preconceptional testing and counseling
a. Blood type, Rh factor, and antibody screen.
b. Rubella and varicella titers.
c. HIV, syphilis, Hepatitis, Neisseria gonorrhoeae and Chlamydia
trachomatis
Selection of Sperm Donors
ī‚—The main qualities to seek in selecting a donor for TDI
are an assurance of good health status and the absence of
known genetic abnormalities.
ī‚—The donor should be of legal age and, ideally, less than 40
years of age.
ī‚—Selection of donors with established fertility is desirable
but not required.
ī‚—Psychological evaluation and counseling
ī‚—The potential impact of the relationship between the
donor and recipient should be explored.
ī‚—No owner, operator, laboratory director, patient's
physician or employee of a facility performing TDI may
serve as a donor in that practice.
Screening and Testing of Sperm Donors
1. Semen testing
ī‚Ą More than one sample be examined (each after a 2- to 5-day
abstinence interval)
ī‚Ą The sample should be examined within 1 to 2 hours
ī‚Ą The minimum criteria for normal semen quality can be applied
2. Genetic evaluation
ī‚Ą Genetic screening for heritable diseases should be performed
ī‚Ą Testing for cystic fibrosis carrier status
3. Medical history
ī‚Ą Donors should be healthy and give no history to suggest hereditary
disease.
ī‚Ą Complete personal and sexual history to exclude high risk for HIV, STIs,
or other infections
4. Physical examination
ī‚Ą Before acceptance, and every 6 months while remaining an active donor,
donors should undergo a complete physical examination
Choosing Donor Characteristics
ī‚—There are several methods for matching the male
partner with the donor.
ī‚—The couple should be encouraged to list the
characteristics that they desire in a prospective
donor
ī‚Ą Race and/or ethnic group, height, body build,
complexion, eye color, and hair color and texture.
ī‚— Consideration should be given to blood type and
Rh factor, particularly for Rh-negative recipients.
The Insemination Procedure &
Pregnancy Rates
ī‚—Insemination may be timed based on a woman’s natural
cycle or in conjunction with an ovulation induction cycle
ī‚—It should occur close to the time of ovulation.
ī‚—The pregnancy rates depend on many factors
ī‚Ą Age of the female recipient
ī‚Ą Presence of other female fertility factors such as
endometriosis, tubal disease, or ovulatory dysfunction
ī‚—the monthly chance of pregnancy ranges from 8% to
15%.
ī‚—The risk of birth defects is no different than natural
conception and is in the range of 2% to 4%.
EMBRYO DONATIONS
EMBRYO DONATION
ī‚—In the current clinical practice of ART, more
embryos than can be transferred safely at one
time commonly are generated
ī‚—These embryos may be cryopreserved for later
transfer
ī‚—Couples who become pregnant and do not desire
another pregnancy, or have other reasons for
choosing not to use their embryos, may have the
option of discarding these embryos or donating
them to other individuals or to research.
Embryo Donation
ī‚—Embryo donation is a form of third party
reproduction.
ī‚—It is a procedure that enables embryos
created by couples undergoing fertility
treatment or created from donor sperm and
donor eggs to be transferred to infertile
patients in order to achieve a pregnancy.
Indications for Embryo Donation
ī‚—Indications for embryo donation
include
ī‚ĄUntreatable infertility that involves both
partners
ī‚Ą Untreatable infertility in a single woman
ī‚Ą Recurrent pregnancy loss thought to be
related to embryonic factors
ī‚ĄGenetic disorders affecting one or both
partners.
Medical and Psychological
Screening of Recipient Couple
ī‚—The process of embryo donation requires that the
recipient couple undergo the appropriate medical
and psychological screening recommended for all
gamete donor cycles.
ī‚— In addition, the female partner undergoes an
evaluation of her uterine cavity and then her
endometrium is prepared with estrogen and
progesterone in anticipation of an embryo transfer.
The Embryo Donation &
Pregnancy Rates
ī‚—Pregnancy following embryo donation
depends on:
ī‚Ą Whether it is fresh or frozen embryo transfer
ī‚Ą The quality of the embryos
ī‚Ą The age of the egg donor & recepient
ī‚Ą And the number of embryos transferred
Ethical and Legal Considerations
ī‚—Embryo donation is a controversial process from both an
ethical as well as a legal standpoint
ī‚—Child born to the couple will have no genetic link with
them
ī‚—Informed consent and counseling be provided to both the
donors of the embryos and the recipient couple to
address all of the potential issues embryo donation might
raise
SURROGACY
Definition
ī‚—The practice of renting a womb and getting a child is like
outsourcing pregnancy
ī‚—The term surrogate is derived from a Latin word subrogare
which means appointed to act in the place of (a woman who
carries a pregnancy for another couple or woman )
ī‚—Surrogacy may be defined as a method of
reproduction whereby a woman agrees to become
pregnant and deliver a child for a contracted party
ī‚—It is both a medically and emotionally complex process that
requires careful evaluation
History
ī‚—The practice of surrogacy first got momentum in
America.
ī‚—Attorney Noel Keane is generally
recognized as the architect of the legal
idea of surrogate motherhood.
ī‚—The issue of surrogacy was widely publicized in
the case of Baby M, in which the surrogate and
biological mother of Melissa Stern ("Baby M"),
born in 1986, refused to give up the custody of
Melissa to the couple with whom she had made
the surrogacy agreement.
Indication of surrogacy
ī‚—Absence of uterus
ī‚Ą Congenital
ī‚Ą Hysterectomy
ī‚—Very small uterus/Non functional Uterus
ī‚Ą Congenital(t shaped & hypoplastic ut)
ī‚Ą Acquired (TB)
ī‚—Woman not able to carry pregnancy
ī‚Ą Danger to the life of the Intended Mother (severe heart,
kidney or respiratory disease, unstable diabetes, or severe
high blood pressure)
ī‚Ą Genetic diseases
ī‚Ą Recurrent abortion
ī‚Ą Recurrent IVF faliure
ī‚—Single father
ī‚—Gay couples.
Types of Surrogacy
ī‚—Traditional surrogacy: Straight or partial
surrogacy
ī‚Ą Surrogate mother inseminated
ī‚Ą She is biological parent and gestational mother
ī‚Ą Baby’s genetic parents are surrogate mother and
commissioning father
ī‚Ą Commissioning mother has to accept child her male
partner fathered with another woman
ī‚—Gestational surrogacy: full or host surrogacy
ī‚Ą Gestational embryo (genetic material) of the couple
ī‚Ą Surrogate mother not genetically related to foetus
ī‚Ą IVF
Types of Surrogacy
ī‚—Altruistic surrogacy:
ī‚Ą Surrogate receives no financial reward for her
pregnancy
ī‚Ą all expenses such as medical expenses, maternity
clothing, and other related expenses related to the
pregnancy and birth are paid by the intended parents
ī‚—Commercial surrogacy:
ī‚Ą surrogates are paid for carrying a child to maturity in
her womb
ī‚Ą This is legal in several countries including in India
The baby born by surrogacy may
be the biological child of:
ī‚—Both parents
ī‚—Mother & sperm donor
ī‚—Surrogate mother & IF (intended father)
ī‚—Neither parent
Steps in Surrogacy
īƒ˜ Proper patient selection
īƒ˜ Source of surrogate (ART bank)
īƒ˜ Proper selection & screening of the surrogate
īƒ˜ Intensive counselling – the key factor
īƒ˜ Synchronizing the cycles of the surrogate and
the genetic mother
īƒ˜ Proper controlled ovarian stimulation and IVF
technique
īƒ˜ Preparing the surrogate
īƒ˜ Window period for embryo transfer
īƒ˜ Taking care of the legalities and financial
contracts
īƒ˜ Transparency of the whole arrangement
Counseling
In depth counseling of all parties engaged in surrogacy
arrangements is of paramount importance and aims to
prepare all parties contemplating this treatment of last
resort to consider all the facts which will have an
influence on the future lives of each of them
Counseling for the couple
īƒ˜ A review of all alternative treatment options
īƒ˜ The practical difficulty and cost of treatment by gestational
surrogacy
īƒ˜ The medical and psychological risks of surrogacy
īƒ˜ Potential psychological risk to the child
īƒ˜ The chances of having a multiple pregnancy
īƒ˜ The degree of involvement that the host may wish to have
with the child
īƒ˜ The possibility that the host may wish to retain the child
after birth
īƒ˜ The possibility that a child may be born with a handicap
īƒ˜ The importance of obtaining legal advice
Selection of Surrogate
īƒ˜Improper selection of the surrogate can create
problems at any stage of the procedure
īƒ˜ART – 2010 has defined the criterias for screening
a surrogate
īƒ˜Indian guidelines for ART ( pending for LAW)
īƒ˜Surrogacy, allowed in India
Counseling for the surrogate
īƒ˜ The full implications of undergoing treatment by IVF
surrogacy
īƒ˜ The possibility of multiple pregnancy
īƒ˜ The possibility of her family and friends being against her
having treatment
īƒ˜ The medical risks associated with pregnancy and delivery
īƒ˜ The implications of guilt on both sides if the host should
spontaneously abort a pregnancy
īƒ˜ The possible effect on her own children of acting as a
surrogate
īƒ˜ The possibility that the host may fell a sense of
bereavement when she gives the baby to the
commissioning couple
Screening for the surrogate
īƒ˜A physical examination and pap smear
īƒ˜Infective disease testing
īƒ˜Hysteroscopy
īƒ˜A mock cycle
īƒ˜Psyclogical testing and evaluation
Agreement /Contract
īƒ˜A legal agreement between a gestational carrier,
her husband if married, and the intended
parents, negotiated by an independent, separate
legal counsel, is highly recommended.
īƒ˜A gestational carrier contract should be as
comprehensive as possible, setting forth for
example, the parties intentions with respect to
the parentage of the child, their financial
arrangements, prenatal care, delivery plans,
selective reduction, abortion, future contact
among the parties, and cooperation on legal steps
to establish parentage.
Surrogacy In India
ī‚—Surrogacy in India is of low cost and the laws are
flexible.
ī‚—Commercial surrogacy is legalized in India since
2002 but there is an immediate need of some
strong legislations
ī‚—In 2008, the Supreme Court of India in the Manji's
case (Japanese Baby) has held that commercial
surrogacy is permitted in India.
ī‚—There is an upcoming Assisted Reproductive
Technology Bill, aiming to regulate the surrogacy
business.
International Surrogacy
ī‚— There is growing evidence that surrogacy in India is
gaining international confidence .
ī‚—Framing international guidelines on the practice of
surrogacy is the challenge of the day.
ī‚— Legal advice and honest counseling to all the parties
engaged in the surrogacy contract with a clear
agreement would be highly beneficial in protecting
surrogacy from exploitation, avoiding legal, social,
and psychological complications and further
promoting the practice.
Costs for surrogacy
īƒ˜The cost of the basic procedure are quite complex
and must be discussed in detail with the patient.
Over and above cost of IVF procedure and
surrogate preparation cost, there can be
ī‚Ą Ongoing psychologic counselling costs
ī‚Ą Pregnancy complications cost
ī‚Ą Maternal complications
ī‚Ą Fetal complications as multiple pregnancy/ selective
fetal reduction
ī‚Ą Genetic amniocentesis if required
ī‚Ą Medical complications
Problems in Surrogacy
īƒ˜When problems arise in surrogacy it is usually
because of a breakdown in communication or
counseling
īƒ˜Issues that need to be comprehensively addressed
are
â€ĸ Medical process
â€ĸ Realistic expectations for all parties
â€ĸ Signing the contract
â€ĸ Potential complications
â€ĸ Financial and legal matters
â€ĸ Establishment of parameters of acceptable conduct
by the parties.
Practical Problems
īƒ˜ What if
ī‚Ą The surrogate is not traceable or refuses to hand over
the child?
ī‚Ą Anomalous baby born ?
ī‚Ą Abortion or preterm delivery?
ī‚Ą Contracts HIV during pregnancy?
ī‚Ą Couple does not come to take the child?
ī‚Ą Couples divorce ?
ī‚Ą Death of comisioning parents ?
ī‚Ą Country of commisiong parents does not allow baby to
enter the country ?
ī‚Ą If it is ED then genetically will not be a DNA match with
parents ? More problems to take the baby to the counrty
of commissioning parents
ī‚Ą Death of the surrogate?
Realistic expectations for all Parties
1. Transparency of the procedure
2. Trust
3. Commitment of all the people involved
4. Respect for one another
5. End result - healthy baby – healthy
surrogate
Well being of the Child
The best interest of the child must always be the
most important consideration in surrogacy
agreements.
Third Party Reproduction
Conclusion
ī‚—Third party parenting represents a significant treatment in
reproductive medicine
ī‚—Extremely favorable success rates can be achieved
ī‚—As technology grows and more awareness is generated, the
ability to offer parenthood to more people also increases
ī‚—Continued attention to personal, moral and ethical issues
should be given to ensure that these treatments are readily
available to those in need of such assistance.
ī‚— Ethical guidelines and appropriate legislations with
contributions from the medical and scientific community
are gradually being established worldwide.
NEW TRENDS
IN ASSISTED REPRODUCTION
New Trends in Assisted Reproduction
īƒ˜ In vitro egg maturation (IVM)
īƒ˜ Assisted Hatching
īƒ˜ Cytoplasmic transfer
īƒ˜ Mild IVF
īƒ˜ Preimplantation Genetic Diagnosis (PGD)
īƒ˜ Frozen Embryo Transfer (FET) / Cryopreservation
īƒ˜ Intra-Cytoplasmic Morphologically Selected Sperm
Injection (IMSI)
īƒ˜ Embryoscope
īƒ˜ Computer Assisted Semen Analysis (CASA)
IN VITRO MATURATION - IVM
ī‚—Mild and safe IVF
ī‚—IVM of human oocytes was suggested in order to
achieve fertilization of immature oocytes retrieved
- during minimally stimulated or unstimulated cycles
- oocytes from PCOS patients to avoid OHSS
- after freezing -thawing of immature oocytes.
- maturation done in specialized culture media
?No advantage in terms of clinical pregnancy and
implantation rates.
Assisted Hatching
Embryo most hatch through the zona pellucida
Defective Hatching may lead to failed
implantation
Assisted Hatching is a micromanipulative
procedure involves slicing, dissolving or making
a small opening in zona pellucida
Helps to increase pregnancy rates by improving
implantation rates.
Indications for Assisted Hatching
Older Age > 38 yrs
Elevated FSH
Egg quantity and quality factor
Embryo quality poor quality embryos
(excessive fragmentation or slow rates of cell
division)
Zona pellucida thickness >17 mm
Previous IVF failures
Cryo-preserved Embryos
Embryo generated from IVM
Assisted Hatching : Methods
The main methods currently
in use for assisted hatching are:
īƒ˜ Chemical
īƒ˜ Mechanical
īƒ˜ Laser –
allows grater degree of control and precision
Blastocyst Transfer
The first IVF human pregnancy was achieved by
blastocyst transfer.
A blastocyst is an embryo that has developed in
culture for at least five days after fertilization
A blastocyst gives a better idea of the competence of an
embryo and has a higher chance of implantation than
a cleaved embryo.
Blastocyst Transfer
ī‚—Conventional Transfer – D2 or D3 : 4 – 8 Cell
ī‚—Availability of more physiological culture
media made extended culture possible
ī‚—Sequential Media – Used here
ī‚—Phase I Sequence –Mimics the nutrients found
in the Fallopian tube
ī‚—Phase II Sequence – Mimics the nutrients
found in the receptive uterine cavity
Blastocyst Transfer - Advantages
1. Embryo selection with highest developmental
potential
2. Synchronization with endometrium
3. Minimize the embryo exposure to the
hyperstimulated uterine environment
4. Reduced embryo expulsion
5. Assessment of true viability after complete genomic
activation
6. Higher implantation – Reduced need of multiple
embryo transfer
7. Increased ability to undergo cryopreservation
8. Ability to undertake cleavage stage embryo biopsy
9. Increased overall efficiency of IVF
Indications of Blastocyt Transfer
Repeated failure to achieve pregnancy
following the transfer of good quality
cleaved embryos
To achieve pregnancy without the risk of
multiple pregnancy.
Patient who do not wish to have their spare
embryos frozen for whatever reasons may
be advised to have blastocyst transfer.
Pre implantation genetic diagnosis
(PGD)
ī‚— PGD is a new technique which combines the recent
advances in molecular genetics and ART.
ī‚— PGD was first reported in 1990.
ī‚— It enables diagnosis of a genetic disorder in an embryo
before its implantation in the uterus.
ī‚— PGD involves embryo biopsy and genetic analysis
which can be performed on
- oocyte /zygote – polar body biopsy
- blastomere from cleavage stage embryo
- trophectoderm biopsy from blastocysts.
Pre implantation genetic
diagnosis (PGD)
ī‚—PGD can be used to detect various diseases like:
ī‚Ą Sickle cell anemia
ī‚Ą Tay-sachs disease
ī‚Ą Haemophilic
ī‚Ą Cystic fibrosis
ī‚—Diagnostic techniques used in PGD are
ī‚Ą PCR
ī‚Ą FISH
ī‚—Following PGD unaffected embryos are transferred back
into the uterine cavity
PGD: Indications
PGD is recommended most frequently for :
ī‚Ą Patient with unexplained infertility
ī‚Ą Recurrent miscarriages
ī‚Ą Unsuccessful IVF cycles
ī‚Ą Advanced maternal age
ī‚Ą Sever male factor infertility
Cryopreservation
īļCryopreservation has become an integral component of
assisted reproductive technology
īļThe slow-freeze and rapid-thaw method used to be the
most common method in cryopreservation
īļVitrification– Cryopreservation using high
concentrations of cryoprotectants to solidify the cell in
a glass state without formation of ice.
īļCryopreservation techniques are being developed for
â€ĸ Gametes (Sperm /Oocytes)
â€ĸ Embryo
â€ĸ Gonadal tissues (Ovarian tissue)
Embryo Cryopreservation
â€ĸ Aim of cryopreservation
To remove as much of intracellular water as in compatible
with life, before freezing, so as to reduce the extent of
intracellular ice formation to point where it ceases to
constitute threat to the viability of the cell.
Freezing of embryos allows significant chance of
pregnancy after single ovarian stimulation
Assuming all embryo survive freeze/thaw process the
patient can undergo 2 cycles of transfer in a typical retrieval
cycle of 15 oocytes
The pregnancy rates of Vitrification technique is promising
Embryo Cryopreservation :
Advantages
Freezing all embryos for subsequent transfer
may be advised for women who are at a high
risk of developing severe ovarian hyperstimulation
syndrome following ovarian stimulation for in-vitro
fertilization (IVF)
When embryo implantation may be compromised in cases such as
the presence of endometrial polyps, poor endometrial development
Difficulty encountered at fresh embryo transfer e.g. cervical
stenosis
Cryopreservation of embryos is very important to be incorporated
in the egg donation programs. It is not always possible to
synchronize the recipient’s cycle with that of the egg donor
Ovarian Tissue Cryopreservation
ī‚—One ovary is removed laparoscopically and ovarian
cortex is isolated
ī‚—Cortex is cut into strips – 10 mm long, 5 mm wide
and 1 mm thickness
ī‚—They are incubated in cryoprotectants and frozen
using a programmable freezer
ī‚—Ethylene glycol (EG) and Dimethyl sulfoxide
(DMSO)are the best cryoprotectants
ī‚—7% of follicles are lost during freezing & thawing
Oocyte Cryopreservation
ī‚—Less effective – Mature oocyte extremely fragile
ī‚—Reasons- Large size, water content & Chromosomal
arrangements
ī‚—Live birth rate /frozen oocyte ~ 3-4%
Cytoplasmic Transfer
īƒ˜ Egg from women undergoing IVF + ooplasma of
donor is fertilized with sperm and resulting
embryo is transferred back
īƒ˜The child will have 3 genetic parent
Mild IVF
In-vitro fertilization is a complex treatment for
infertility that entails
costly regimens for ovarian stimulation
serious discomfort to patients by daily injections
multiple pregnancies
ovarian hyperstimulation syndrome (OHSS)
This has led to the development of mild in vitro
fertilization (IVF) Treatment protocol which
includes
ī‚Ą Mild stimulation protocol
ī‚Ą Single embryo transfer i.e. usually blastocyst
Bioactive therapeutic preparations may
revolutionize IVF treatment in near future
INTRA-CYTOPLASMIC
MORPHOLOGICALLY SELECTED SPERM
INJECTION (IMSI)
īļIntroduction of ICSI revolutionized the treatment of
male factor infertility.
īļICSI involves the microinjection of a single sperm into
an egg
IMSI helps to select best sperms based on
morphology to improve the success and is said to be
more beneficial than ICSI in patients with
Two previous IVF or ICSI failures
Unexplained infertility
Severe male factor infertility
Better advantage in terms of higher pregnancy rate and
lower miscarriage rates.
INTRA-CYTOPLASMIC
MORPHOLOGICALLY SELECTED SPERM
INJECTION (IMSI)
The IMSI method was first developed in 2004 by a
team led by Benjamin Bartoov, in Israel.
IMSI is, becoming the most efficient variant of
micromanipulation-assisted fertilization.
It helps in magnifying the image of the sperm 7,200
times, thereby allowing to pick the best looking
morphologically healthier sperms.
advanced version of ICSI having the magnification
capacity of 16 times higher than ICSI.
IMSI VS ICSI
Spindle View
ī‚—Each egg has mitotic spindle
ī‚—Chromosome spindle can now be visualized, while actually
injecting the eggs.
ī‚—This would prevent egg damage, increase fertilization
rates, increase embryo formation rates and improve
embryo quality
ī‚—Any abnormality of spindle has high risk for developing
into embryos with chromosomal abnormalities may result
in failed fertilization, poor embryo development, failed
implantation or spontaneous abortion
Embryoscope
EmbryoScope is a novel embryo monitoring system
for assessing embryo quality.
Using Leica optics it provides continuous control
and recording of embryo development and
provides
respiration rates of single embryos during development
image acquisition of embryo development
onset and duration of cell divisions
In future Embryoscope may replace the classical microscope
based methods for selecting embryos
EMBRYOSCOPE : EMBRYO MONITORING SYSTEM
Proteomics :
Embryo Selection in IVF
ī‚—Embryo is an active participant in the process of
implantation
ī‚—It secretes various proteins that can be detected in
the culture medium
ī‚—Mass spectrometry have made it possible to analyze
extremely small amounts of biological secretions
ī‚—The protein profile can be used to differentiate
between good-quality and degenerating blastocysts
ī‚—Specific proteins were found to be secreted in larger
amounts by good-quality embryos (ie, platelet-
activating factor, leptin, acrogranin, HLA-G)
Computer Assisted Semen Analysis
(CASA)
ī‚—CASA refers to an automated system
(hardware and software) to visualize and digitize
successive images of sperm and it’s process.
ī‚—Analyzes the information, and provide accurate,
precise, and meaningful information on the
kinematics of individual sperm cells (count,
motility and morphology)
ī‚—Provides fast, accurate and objectively repeatable
results in a complete report.
ī‚—Makes the assessment of semen quality more
subjective and detailed.
Why CASA ?
ī‚—Sperm concentration and motility measurements
are least reliable with current manual methods.
ī‚—Manual semen analysis is associated with large
inter-laboratory variation.
ī‚—Impossible to compare sperm motility assessments
of different laboratories.
ī‚—More detailed description of sperm movements is
not possible with manual method (only 4
categories).
Key Feature of CASA
ī‚—Calculate the spermatic Counts &
Concentrations of a sample
ī‚—Detailed results on Motility & Progressive
Motility, velocities, motion characteristic
ī‚—Morphology and morphometry
ī‚—DNA fragmentation study
ART Success Rates
30%-40% of women who start each cycle of
treatment achieve clinical pregnancy.
Success rates have gone up beyond 50% in last
5 yrs.
It depends on:
īƒ˜ Age
īƒ˜ Cause of infertility
īƒ˜ Response to ovarian stimulation
īƒ˜ Semen quality
īƒ˜ Appearance of embryo generated and transferred
Arpit Test Tube Baby Centre
Record of IVF cases in last 12 years
ī‚Ą 3596 IVF cases
ī‚Ą 1876 cilinical pregnancy ;
Overall Success rate 52.18%
ī‚Ą 54 ectopic pregnancies 2.87%
ī‚Ą 221abortions 11.8%
Take home baby rate 38.44%
Conclusions
Significant advances have been made in assisted reproductive
technology since the birth of the first test tube baby
Increasing number of women is experiencing infertility today than in
the past decades.
Third party reproduction has become an important therapeutic option
and, at times, the only option for couples seeking fertility treatment.
New trends in ART have revolutionised the reproductive medicine in
last one decade
These new technologies have also improved success rates in ART
Milder ovarian stimulation regimens are gaining acceptance and will
likely be more widely used in years to come.
Improved access and affordability of ART is the demand of the
developing nation
Thank you for
your
patient hearing

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THIRD PARTY REPRODUCTION GUIDE

  • 1. THIRD PARTY REPRODUCTION & CURRENT CONCEPTS IN ART DR. VANDANA BANSAL MS, D.PHIL.(GOLD MEDALIST), DGO, FCGP Senior Gynaecologist & Obstetrician Infertility & IVF Specialist Director Vandana Women’s Hospital Arpit Test Tube Baby Centre Jeevan Jyoti Hospital
  • 2. Introduction ī‚—The process of reproduction has long fascinated man kind particularly from scientific perspectives. ī‚—The sole objective of any living organism is to procreate i.e. to reproduce itself. ī‚—With an average monthly fecundity rate of 20%, human beings are not fertile mammals. ī‚—10-15% of couples has difficulties in conceiving and seeks special fertility care at least once during their reproductive life time.
  • 3. Infertility Infertility is defined as a failure to conceive within one year of regular unprotected coitus – Primary Infertility – patient’s who have never conceived – Secondary Infertility – indicates previous pregnancy but failure to conceive subsequently’. 80% of couple conceive within 1st year 10% conceive by the end of 2nd year 10% remain infertile by end of 2nd year Incidence - 10% to 15%
  • 4. Infertility Prevalence and Overview of Treatments ī‚—The overall incidence of infertility has remained relatively unchanged for the past 30 years (Speroff & Fritz, 2005). ī‚—Approximately half of all women who receive fertility care achieve conception leading to a live birth (Speroff & Fritz, 2005).
  • 5. Causes of Infertility Female factor Ovulatory dysfunction Cervical factors Tubal factors Endometriosis Uterine factors – Fibroid uterus, Uterine Synechiae, Congenital malformation of uterus Vaginal factors – Vaginal Atresia, Septate vagina Immunological Coital problem Hormonal Unexplained Male factor Defective spermatogenesis Abnormal Semen Parameters Obstruction of the duct Failure to deposit sperm high in the vagina Idiopathic Varicocele Hormonal Systemic causes Immunological
  • 6. Origin of Reproduction So, God created man in His own image, in the image of God created He him; male and female created. And God blessed them and God said unto them. Be fruitful and multiply and replenish the earth and Subdue it. (Genesis 1:27-28)
  • 7. Treatment Optionsâ€Ļ Overcoming Infertility Nearly 90% of all infertility cases, both male and female factor, can be successfully treated. Treatment options are: īƒ˜ Ovulation Induction īƒ˜ Medical & Surgical treatment of Male īƒ˜ Laparoscopic & Hysteroscopic Surgery for Female īƒ˜ Intrauterine Insemination (IUI) īƒ˜ Assisted Reproductive Technology (ART) īƒ˜ Third party Reproduction
  • 8. Human Reproduction – Changed ī‚—25th July, 1978 ī‚—Louise Joy Brown ī‚—World’s First Successful Test Tube Baby Landmark Event in Reproductive Revolution Science Proves Wonders
  • 9. Third Party Reproduction ī‚—Third party reproduction refers to the use of oocytes, sperm, embryos, or uterus that has been provided by a third person (donor) to enable an infertile individual or couple (intended parent) to become parents. ī‚—Ethical, moral, religious and legal concerns play a significant role in these treatments ī‚—They have allowed the miracle of childbirth to those who might otherwise be unable to achieve this goal.
  • 10. With increasing age, the woman’s ovaries run out of eggs(limited ovarian reserve) The only option these women have for having a baby is IVF egg donation â€Ļthird party
  • 11. There is also an increasing incidence of Premature Ovarian Failure & Diminished Ovarian Reserve ī‚—For these women to concieve the only way out is to use donor eggs(third party) ī‚—Aged women ī‚—Oophrectomy cases ī‚—Cancer ovary and operated or irradiated ī‚—Premature ovarian failure(premature menopause)
  • 12. There is an increasing incidence of non obstructive azospermia The only chance these couple have to have a baby is through sperm donationâ€Ļâ€Ļthird party
  • 13. Some women have untreatable uterine abnormality RKH, endometrial TB, hystrectomy, etc
  • 14. The only chance of these couples to have babies is through â€Ļâ€Ļ..â€Ļâ€Ļ â€Ļâ€Ļâ€Ļâ€Ļâ€Ļthird party reproduction
  • 15. Indications for Third-party reproduction Women without functional ovaries ī‚—Advanced maternal age ī‚—Surgical or natural menopause ī‚—Premature ovarian failure ī‚—Previous chemotherapy or radiotherapy ī‚—Women born without functional ovaries Women with functional ovaries ī‚—Recurrent pregnancy loss ī‚—Repetitive IVF failures/poor response ī‚—Women without functioning uterus ī‚—Uterus that is unsuitable for pregnancy such as extensive fibroids, adenomyosis, or Asherman’s ī‚—Women with a serious medical condition that increases significant morbidity, or even mortality if pregnancy occurs ī‚—Inheritable disorders Male & Female same sex couple
  • 16. Types of Third Party Reproduction īļOocyte donation īļSperm Donation īļEmbryo Donation īļSurrogacy īļ Traditional surrogacy īļ Gestational surrogacy
  • 17. What is Oocyte Donation? ī‚— Egg donation is the part of third party reproduction.Egg donation is the part of third party reproduction. ī‚— Eggs are retrieved from a young woman ( < 33 yrs ) calledEggs are retrieved from a young woman ( < 33 yrs ) called the donor.the donor. ī‚— These eggs are fertilized with the sperms of the recipient’sThese eggs are fertilized with the sperms of the recipient’s husband.husband. ī‚— Resultant embryo is transferred to the uterus of theResultant embryo is transferred to the uterus of the recipient.recipient.
  • 18. Oocyte Donation ī‚—Oocyte donation has been used for more than 20 years to help infertile couples become pregnant through IVF ī‚—The first pregnancy achieved with egg donation was reported in 1984. ī‚—Oocyte from a donor are fertilized with male partner’s sperm & resulting embryos are transferred into the female partner’s uterus
  • 19. Oocyte Donation: Indications Women without ovarian function: ī‚— Advanced maternal age ī‚— Surgical or natural menopause ī‚— Premature ovarian failure ī‚— Women born without functional ovaries ī‚— Previous chemotherapy or radiotherapy Women with ovarian function: ī‚— Recurrent pregnancy loss ī‚— Repetitive IVF failures/poor response ī‚— Inheritable disorders Male same sex couple
  • 20. The Oocyte Donation Process The recipient couple ī‚—Psychological issues ī‚—Medical Screening ī‚—Legal Issues ī‚—Ethical concerns The donor ī‚—Donor recruitment ī‚—Donor Screening ī‚—Donor matching
  • 21. Psychological consultation for oocyte donor recipients ī‚—The decision to proceed with donated oocytes is complex, and patients and their partners (if applicable) may benefit from psychological counseling ī‚—clinician should strongly recommend psychological counseling by a qualified mental health professional ī‚—The assessment should include a clinical interview and, where appropriate, psychological testing. ī‚—In cases of directed donation, the potential impact of the relationship between the donor and recipient should be explored
  • 22. Evaluation of the oocyte recipient A. Medical and reproductive history B. A complete general physical examination including a pelvic examination. C. Assessment of the uterine cavity (HSG, saline infusion ultrasonography) D. Standard preconceptional testing and counseling a. Blood type, Rh factor, and antibody screen. b. Rubella and varicella titers. c. HIV, syphilis, Hepatitis, Neisseria gonorrhoeae and Chlamydia trachomatis
  • 23. Evaluation of the partner of the oocyte recipient 1. Semen analysis for male partners. 2. Blood type and Rh factor. 3. Serologic test for syphilis. 4. Hepatitis B surface antigen. 5. Hepatitis B core antibody (IgG and IgM). 6. Hepatitis C antibody and NAT. 7. HIV-1 (AB and NAT), HIV-2 AB testing 8. Appropriate genetic screening and testing based on history
  • 24. Classification of Donors Oocyte donors can be classified based on the anonymity of their identity. ī‚—Anonymous Donors: ī‚Ą Recruited and screened by the ART program or by a private agency. ī‚—Directed donors: ī‚Ą Generally recruited by the recipients, and screened by agencies or centers ī‚Ą The donor is generally a close relative or friend ī‚—IVF programs: ī‚Ą Women undergoing IVF may agree to donate their excess eggs to infertile patients
  • 25. Donors ī‚—IVF patients, willing to share their extra- oocytes (OOCYTE SHARING PROGRAMME( COMMON ) ī‚—Women with tubectomy, willing to be hyperstimulated ( MONETARY COMPENSATION) ī‚—Known donors include family members who come forward to donate their oocytes ( FAMILY ) ī‚—Professional donors, recruited after advertisement (MONETARY COMPENSATION) ī‚—Volunteers , philanthropic enough to donate their oocytes (RARE BUT MAY FIND SUCH)
  • 26. Selection of Donors ī‚— Oocyte donation may be undertaken with known or anonymous ī‚— Psychological evaluation and counseling ī‚— Oocyte donors should be of legal age (21 - 34 years). ī‚— Donors less than 21 years of age should have psychological evaluation and decision should be on an individual basis. ī‚— If a donor is over 34 yr, it should be revealed to recipient concerning cytogenetic risks and pregnancy rates. ī‚— Proven fertility in the donor is desirable ī‚— The donor should undergo appropriate genetic evaluation ī‚— If sharing of oocytes is contemplated, informed consent must be obtained
  • 27. Donor Screening ī‚—Suggested medical ,personal, family (genetic) & reproductive history ī‚—Complete blood count with platelets ī‚—Blood type ī‚—Hepatitis screen ī‚—VDRL ī‚—HIV-1, HIV- 2 ī‚—Cervical cultures for gonorrhoea and Chlamydia ī‚—Pap smear ī‚—Transvaginal ultrasound of pelvis ī‚—Appropriate genetic tests Proper selection of donor thorough evaluation & treatmentProper selection of donor thorough evaluation & treatment of recipient. Optimum dose of Gonadotrophins and properof recipient. Optimum dose of Gonadotrophins and proper monitoring of donor avoid complications in egg donor.monitoring of donor avoid complications in egg donor.
  • 28. Matching the Intended Parent to an Oocyte Donor ī‚—Donors are matched as closely as possible with the recipient couple for characteristics, such as hair color, eye color, ancestry; occupation, educational level; previous donation history ī‚—Medical matching (Blood group & other diseases) ī‚—Compensated for their time & effort ī‚— Compensation remains the same no matter how many oocytes are retrieved
  • 29. Algorithm of Oocyte Donation Recipient evaluation(USG to monitor development of oocytes, blood tests to check E2 levels). ↓ Donor Recruitment ↓ Donor Screening ↓ Obtaining informed consent from recipient and donor ↓ Synchronization of donor and recipient cycles ↓ Prescription of hormones for the recipient ↓ Ovarian stimulation of donor ↓ Oocytes retrieval from donors ↓ Fertilization of oocytes ↓ Embryo Transfer ↓ Maintenance of pregnancy in recipient
  • 30. Donor Treatment Cycle Synchronisation ī‚—The synchronization of cycles in the donor and recipient is extremely important to the success of the oocyte donation. ī‚—The treatment cycles of the oocyte donor and the cycling recipients involve pituitary suppression by GnRH agonist ī‚—Alternative protocols using GnRH antagonist can also be used.
  • 31. Egg Donation Treatment Sequence Actual treatment is individualized
  • 32. Schematic Diagram of an Oocyte Donor Stimulation Protocol Alternative protocols using GnRH antagonist can also be used
  • 33. Ovum Pick Up ī‚—Approximately 36 hours after the hCG injection ī‚—Short G/A anesthesia ī‚—TVS aspiration is done with needle connected to aspiration pump ī‚—Identification of oocytes is done in Lab simultaneously ī‚—Earlier laparoscopic aspiration was done ī‚—Antibiotic cover is given for 5 days ī‚—Patient can go home after 3-4 hours
  • 34. Protocol for Recipient ī‚—The uterus is prepared using hormones (estrogen and progesterone) to mimic the natural menstrual cycle ī‚— GnRHa is used to suppress the pituitary gland to prevent the patient from ovulating during the preparation of the uterus ī‚—Once the pituitary gland is suppressed, exogenous estrogen is given & in turn it thickens the uterine lining ī‚— Pills, Patches, or even Injections ī‚—Progesterone started once endometrium is >8mm & on the day of oocyte retrieval in donor ī‚— Vaginal suppository or Gel or as Injections ī‚—The no. of days progesterone is given before the transfer must match the stage of embryo development
  • 35. Schematic Diagram of a Recipient Protocol. â€ĸIf the pregnancy test is positive, recipients are asked to continue the estrogen and progesterone replacement until 10 weeks of gestation. â€ĸIf the pregnancy test is negative, patient can stop the hormonal replacement. E – estrogen; P –progesterone.
  • 36. Endometrial Receptivity īļ Endometrial receptivity is the window of time when the uterine environment is conductive to embryo acceptance and subsequent implantation īļ Timely expression of a number of complex molecules like hormones, cytokines & growth factors, and their crosstalk play a crucial role in preparing receptive endometrium īļ Endometrial histology is influenced by estradiol & progesterone and their synchronization is essential for implantation window īļ Parameters for assessing endometrial receptivity include: īƒ˜ endometrial thickness (>7 - <14 mm) īƒ˜ endometrial pattern (triple-line pattern) īƒ˜ endometrial and subendometrial blood flow (within Zone 3 )
  • 37. Window of Receptivity ī‚—The condition of uterus becomes optimal for implantation for a brief period during leuteal phase known as Window of receptivity ī‚—Short - last for 4 days (Day 20-24 of the menstrual cycle) ī‚Ą +6 to 10 (Bergh and Navot 1992) ī‚Ą +3.5 (Rogers 1989) ī‚Ą +5 to 7 (Psychoyochos 1993) ī‚—During this period endometrium undergoes important changes that makes it receptive to the implanting embryo ī‚—Key factor in implantation is the synchrony between embryo development & endometrial receptivity Post ovulatory Days
  • 38. WINDOW OF RECEPTIVITY (Implantation Window) JARVELA et al 2005;
  • 39. Luteal Phase Support īļ Vaginal progestin Pressaries īļ 100 BD- if CC/FSH/HMG cycle īļ 200 TDS- if GnRHa+HMG/FSH īļ Oral – Dehydrogestone 10 mg BD īļ HCG 2000-2500 IU IM day 3 īļ Progesterone – 50-100 mg IM Rationale and Indications â€ĸ COH results in abnormal endometrial Development â€ĸ High level of estrogen seen in COH may cause premature luteolysis â€ĸ Pituitary down regulation with GnRHa is detrimental to luteal phase â€ĸ Ovarian aspiration disrupts granulosa cells â€ĸ Important to synchronise embryo and endometrium for successful implantation
  • 40. Concerns & Complications â€ĸ Ethical, legal, religious & social issues â€ĸ Relationship between biological & social parents, & safeguarding of the interests of the off spring, may be resolved by specific legislation pertaining to each country â€ĸ Adequate study of the health risks of oocyte extraction, including long-term risks â€ĸ Medical costs for adverse effects caused by the procedure â€ĸ True informed consent from women who provide oocytes â€ĸ Exploitation of poor women â€ĸ No meaningful oversight
  • 41. Pregnancy Rates with Egg Donation Depends on: ī‚—Age of the Donor & Recipient ī‚—Cause of the couple's infertility ī‚—Quality & Developmental stage and number of embryos transferred ī‚—Average live-birth rate per fresh embryo transfer is 55.1% (CDC , 2009) ī‚—The major risk for egg-donor programs is multiple gestations- 39.9% (CDC, 2009)
  • 42. Legal Issues ī‚—Egg donation raises questions regarding all four of the basic principles of medical ethics: autonomy, justice, beneficence, and non-maleficence. ī‚—Infertility specialists must consider these conflicts of interest. ī‚—Egg donation is regulated and / or prohibited in many countries. ī‚—The egg recipient and the father of the child are the legal parents. ī‚—Most egg donors express a strong desire not to be identified by the children. ī‚—Should donor identity be revealed to egg donation child once he/she reaches the age of 18 years??
  • 43.
  • 45. Sperm Donation ī‚— Artificial insemination using donor sperm has been practiced for over a century. ī‚— The first published reports about the practice were in 1945. ī‚— Over the past 10 years, the utilization of donor sperm has decreased due to use of ICSI ī‚— Since the late 1980s, with the emergence of AIDS artificial donor insemination has been performed exclusively with frozen and quarantined sperm. ī‚— Current FDA and ASRM guidelines recommend that sperm be quarantined for at least six months before being released for use ī‚— Therapeutic donor insemination (TDI) may be used to achieve pregnancy where appropriate indications exist.
  • 46. Indications for Sperm Donation Therapeutic donor insemination (DI or TDI) is appropriate in ī‚— Severe abnormalities in the semen Parameters ī‚— Azoospermia : congenital or acquired. ī‚Ą Obstructive azoospermia ī‚Ą Non-obstructive azoospermia ī‚— Severe oligospermia ī‚— Seminal fluid abnormalities ī‚— Single woman desiring pregnancy ī‚— Lesbians ī‚— DI is also indicated if the ī‚Ą male has ejaculatory dysfunction ī‚Ą male has significant genetic defect ī‚Ą female is Rh-sensitized and the male partner is Rh-positive.
  • 47. Psychological Consultation for Recipients ī‚—The decision to proceed with donor insemination is complex , may benefit from psychological counseling ī‚—The clinician should strongly recommend psychological counseling by a qualified mental health professional ī‚—In cases of directed donation, the potential impact of the relationship between the donor and recipient should be explored
  • 48. Evaluation of the Female Recipient A. Medical and reproductive history B. A complete general physical examination including a pelvic examination. C. Assessment of the uterine cavity (HSG, saline infusion ultrasonography) D. Standard preconceptional testing and counseling a. Blood type, Rh factor, and antibody screen. b. Rubella and varicella titers. c. HIV, syphilis, Hepatitis, Neisseria gonorrhoeae and Chlamydia trachomatis
  • 49. Selection of Sperm Donors ī‚—The main qualities to seek in selecting a donor for TDI are an assurance of good health status and the absence of known genetic abnormalities. ī‚—The donor should be of legal age and, ideally, less than 40 years of age. ī‚—Selection of donors with established fertility is desirable but not required. ī‚—Psychological evaluation and counseling ī‚—The potential impact of the relationship between the donor and recipient should be explored. ī‚—No owner, operator, laboratory director, patient's physician or employee of a facility performing TDI may serve as a donor in that practice.
  • 50. Screening and Testing of Sperm Donors 1. Semen testing ī‚Ą More than one sample be examined (each after a 2- to 5-day abstinence interval) ī‚Ą The sample should be examined within 1 to 2 hours ī‚Ą The minimum criteria for normal semen quality can be applied 2. Genetic evaluation ī‚Ą Genetic screening for heritable diseases should be performed ī‚Ą Testing for cystic fibrosis carrier status 3. Medical history ī‚Ą Donors should be healthy and give no history to suggest hereditary disease. ī‚Ą Complete personal and sexual history to exclude high risk for HIV, STIs, or other infections 4. Physical examination ī‚Ą Before acceptance, and every 6 months while remaining an active donor, donors should undergo a complete physical examination
  • 51. Choosing Donor Characteristics ī‚—There are several methods for matching the male partner with the donor. ī‚—The couple should be encouraged to list the characteristics that they desire in a prospective donor ī‚Ą Race and/or ethnic group, height, body build, complexion, eye color, and hair color and texture. ī‚— Consideration should be given to blood type and Rh factor, particularly for Rh-negative recipients.
  • 52. The Insemination Procedure & Pregnancy Rates ī‚—Insemination may be timed based on a woman’s natural cycle or in conjunction with an ovulation induction cycle ī‚—It should occur close to the time of ovulation. ī‚—The pregnancy rates depend on many factors ī‚Ą Age of the female recipient ī‚Ą Presence of other female fertility factors such as endometriosis, tubal disease, or ovulatory dysfunction ī‚—the monthly chance of pregnancy ranges from 8% to 15%. ī‚—The risk of birth defects is no different than natural conception and is in the range of 2% to 4%.
  • 54. EMBRYO DONATION ī‚—In the current clinical practice of ART, more embryos than can be transferred safely at one time commonly are generated ī‚—These embryos may be cryopreserved for later transfer ī‚—Couples who become pregnant and do not desire another pregnancy, or have other reasons for choosing not to use their embryos, may have the option of discarding these embryos or donating them to other individuals or to research.
  • 55. Embryo Donation ī‚—Embryo donation is a form of third party reproduction. ī‚—It is a procedure that enables embryos created by couples undergoing fertility treatment or created from donor sperm and donor eggs to be transferred to infertile patients in order to achieve a pregnancy.
  • 56. Indications for Embryo Donation ī‚—Indications for embryo donation include ī‚ĄUntreatable infertility that involves both partners ī‚Ą Untreatable infertility in a single woman ī‚Ą Recurrent pregnancy loss thought to be related to embryonic factors ī‚ĄGenetic disorders affecting one or both partners.
  • 57. Medical and Psychological Screening of Recipient Couple ī‚—The process of embryo donation requires that the recipient couple undergo the appropriate medical and psychological screening recommended for all gamete donor cycles. ī‚— In addition, the female partner undergoes an evaluation of her uterine cavity and then her endometrium is prepared with estrogen and progesterone in anticipation of an embryo transfer.
  • 58. The Embryo Donation & Pregnancy Rates ī‚—Pregnancy following embryo donation depends on: ī‚Ą Whether it is fresh or frozen embryo transfer ī‚Ą The quality of the embryos ī‚Ą The age of the egg donor & recepient ī‚Ą And the number of embryos transferred
  • 59. Ethical and Legal Considerations ī‚—Embryo donation is a controversial process from both an ethical as well as a legal standpoint ī‚—Child born to the couple will have no genetic link with them ī‚—Informed consent and counseling be provided to both the donors of the embryos and the recipient couple to address all of the potential issues embryo donation might raise
  • 61. Definition ī‚—The practice of renting a womb and getting a child is like outsourcing pregnancy ī‚—The term surrogate is derived from a Latin word subrogare which means appointed to act in the place of (a woman who carries a pregnancy for another couple or woman ) ī‚—Surrogacy may be defined as a method of reproduction whereby a woman agrees to become pregnant and deliver a child for a contracted party ī‚—It is both a medically and emotionally complex process that requires careful evaluation
  • 62. History ī‚—The practice of surrogacy first got momentum in America. ī‚—Attorney Noel Keane is generally recognized as the architect of the legal idea of surrogate motherhood. ī‚—The issue of surrogacy was widely publicized in the case of Baby M, in which the surrogate and biological mother of Melissa Stern ("Baby M"), born in 1986, refused to give up the custody of Melissa to the couple with whom she had made the surrogacy agreement.
  • 63. Indication of surrogacy ī‚—Absence of uterus ī‚Ą Congenital ī‚Ą Hysterectomy ī‚—Very small uterus/Non functional Uterus ī‚Ą Congenital(t shaped & hypoplastic ut) ī‚Ą Acquired (TB) ī‚—Woman not able to carry pregnancy ī‚Ą Danger to the life of the Intended Mother (severe heart, kidney or respiratory disease, unstable diabetes, or severe high blood pressure) ī‚Ą Genetic diseases ī‚Ą Recurrent abortion ī‚Ą Recurrent IVF faliure ī‚—Single father ī‚—Gay couples.
  • 64. Types of Surrogacy ī‚—Traditional surrogacy: Straight or partial surrogacy ī‚Ą Surrogate mother inseminated ī‚Ą She is biological parent and gestational mother ī‚Ą Baby’s genetic parents are surrogate mother and commissioning father ī‚Ą Commissioning mother has to accept child her male partner fathered with another woman ī‚—Gestational surrogacy: full or host surrogacy ī‚Ą Gestational embryo (genetic material) of the couple ī‚Ą Surrogate mother not genetically related to foetus ī‚Ą IVF
  • 65. Types of Surrogacy ī‚—Altruistic surrogacy: ī‚Ą Surrogate receives no financial reward for her pregnancy ī‚Ą all expenses such as medical expenses, maternity clothing, and other related expenses related to the pregnancy and birth are paid by the intended parents ī‚—Commercial surrogacy: ī‚Ą surrogates are paid for carrying a child to maturity in her womb ī‚Ą This is legal in several countries including in India
  • 66. The baby born by surrogacy may be the biological child of: ī‚—Both parents ī‚—Mother & sperm donor ī‚—Surrogate mother & IF (intended father) ī‚—Neither parent
  • 67. Steps in Surrogacy īƒ˜ Proper patient selection īƒ˜ Source of surrogate (ART bank) īƒ˜ Proper selection & screening of the surrogate īƒ˜ Intensive counselling – the key factor īƒ˜ Synchronizing the cycles of the surrogate and the genetic mother īƒ˜ Proper controlled ovarian stimulation and IVF technique īƒ˜ Preparing the surrogate īƒ˜ Window period for embryo transfer īƒ˜ Taking care of the legalities and financial contracts īƒ˜ Transparency of the whole arrangement
  • 68. Counseling In depth counseling of all parties engaged in surrogacy arrangements is of paramount importance and aims to prepare all parties contemplating this treatment of last resort to consider all the facts which will have an influence on the future lives of each of them
  • 69. Counseling for the couple īƒ˜ A review of all alternative treatment options īƒ˜ The practical difficulty and cost of treatment by gestational surrogacy īƒ˜ The medical and psychological risks of surrogacy īƒ˜ Potential psychological risk to the child īƒ˜ The chances of having a multiple pregnancy īƒ˜ The degree of involvement that the host may wish to have with the child īƒ˜ The possibility that the host may wish to retain the child after birth īƒ˜ The possibility that a child may be born with a handicap īƒ˜ The importance of obtaining legal advice
  • 70. Selection of Surrogate īƒ˜Improper selection of the surrogate can create problems at any stage of the procedure īƒ˜ART – 2010 has defined the criterias for screening a surrogate īƒ˜Indian guidelines for ART ( pending for LAW) īƒ˜Surrogacy, allowed in India
  • 71. Counseling for the surrogate īƒ˜ The full implications of undergoing treatment by IVF surrogacy īƒ˜ The possibility of multiple pregnancy īƒ˜ The possibility of her family and friends being against her having treatment īƒ˜ The medical risks associated with pregnancy and delivery īƒ˜ The implications of guilt on both sides if the host should spontaneously abort a pregnancy īƒ˜ The possible effect on her own children of acting as a surrogate īƒ˜ The possibility that the host may fell a sense of bereavement when she gives the baby to the commissioning couple
  • 72. Screening for the surrogate īƒ˜A physical examination and pap smear īƒ˜Infective disease testing īƒ˜Hysteroscopy īƒ˜A mock cycle īƒ˜Psyclogical testing and evaluation
  • 73. Agreement /Contract īƒ˜A legal agreement between a gestational carrier, her husband if married, and the intended parents, negotiated by an independent, separate legal counsel, is highly recommended. īƒ˜A gestational carrier contract should be as comprehensive as possible, setting forth for example, the parties intentions with respect to the parentage of the child, their financial arrangements, prenatal care, delivery plans, selective reduction, abortion, future contact among the parties, and cooperation on legal steps to establish parentage.
  • 74. Surrogacy In India ī‚—Surrogacy in India is of low cost and the laws are flexible. ī‚—Commercial surrogacy is legalized in India since 2002 but there is an immediate need of some strong legislations ī‚—In 2008, the Supreme Court of India in the Manji's case (Japanese Baby) has held that commercial surrogacy is permitted in India. ī‚—There is an upcoming Assisted Reproductive Technology Bill, aiming to regulate the surrogacy business.
  • 75. International Surrogacy ī‚— There is growing evidence that surrogacy in India is gaining international confidence . ī‚—Framing international guidelines on the practice of surrogacy is the challenge of the day. ī‚— Legal advice and honest counseling to all the parties engaged in the surrogacy contract with a clear agreement would be highly beneficial in protecting surrogacy from exploitation, avoiding legal, social, and psychological complications and further promoting the practice.
  • 76. Costs for surrogacy īƒ˜The cost of the basic procedure are quite complex and must be discussed in detail with the patient. Over and above cost of IVF procedure and surrogate preparation cost, there can be ī‚Ą Ongoing psychologic counselling costs ī‚Ą Pregnancy complications cost ī‚Ą Maternal complications ī‚Ą Fetal complications as multiple pregnancy/ selective fetal reduction ī‚Ą Genetic amniocentesis if required ī‚Ą Medical complications
  • 77. Problems in Surrogacy īƒ˜When problems arise in surrogacy it is usually because of a breakdown in communication or counseling īƒ˜Issues that need to be comprehensively addressed are â€ĸ Medical process â€ĸ Realistic expectations for all parties â€ĸ Signing the contract â€ĸ Potential complications â€ĸ Financial and legal matters â€ĸ Establishment of parameters of acceptable conduct by the parties.
  • 78. Practical Problems īƒ˜ What if ī‚Ą The surrogate is not traceable or refuses to hand over the child? ī‚Ą Anomalous baby born ? ī‚Ą Abortion or preterm delivery? ī‚Ą Contracts HIV during pregnancy? ī‚Ą Couple does not come to take the child? ī‚Ą Couples divorce ? ī‚Ą Death of comisioning parents ? ī‚Ą Country of commisiong parents does not allow baby to enter the country ? ī‚Ą If it is ED then genetically will not be a DNA match with parents ? More problems to take the baby to the counrty of commissioning parents ī‚Ą Death of the surrogate?
  • 79. Realistic expectations for all Parties 1. Transparency of the procedure 2. Trust 3. Commitment of all the people involved 4. Respect for one another 5. End result - healthy baby – healthy surrogate
  • 80. Well being of the Child The best interest of the child must always be the most important consideration in surrogacy agreements.
  • 81. Third Party Reproduction Conclusion ī‚—Third party parenting represents a significant treatment in reproductive medicine ī‚—Extremely favorable success rates can be achieved ī‚—As technology grows and more awareness is generated, the ability to offer parenthood to more people also increases ī‚—Continued attention to personal, moral and ethical issues should be given to ensure that these treatments are readily available to those in need of such assistance. ī‚— Ethical guidelines and appropriate legislations with contributions from the medical and scientific community are gradually being established worldwide.
  • 82. NEW TRENDS IN ASSISTED REPRODUCTION
  • 83. New Trends in Assisted Reproduction īƒ˜ In vitro egg maturation (IVM) īƒ˜ Assisted Hatching īƒ˜ Cytoplasmic transfer īƒ˜ Mild IVF īƒ˜ Preimplantation Genetic Diagnosis (PGD) īƒ˜ Frozen Embryo Transfer (FET) / Cryopreservation īƒ˜ Intra-Cytoplasmic Morphologically Selected Sperm Injection (IMSI) īƒ˜ Embryoscope īƒ˜ Computer Assisted Semen Analysis (CASA)
  • 84. IN VITRO MATURATION - IVM ī‚—Mild and safe IVF ī‚—IVM of human oocytes was suggested in order to achieve fertilization of immature oocytes retrieved - during minimally stimulated or unstimulated cycles - oocytes from PCOS patients to avoid OHSS - after freezing -thawing of immature oocytes. - maturation done in specialized culture media ?No advantage in terms of clinical pregnancy and implantation rates.
  • 85. Assisted Hatching Embryo most hatch through the zona pellucida Defective Hatching may lead to failed implantation Assisted Hatching is a micromanipulative procedure involves slicing, dissolving or making a small opening in zona pellucida Helps to increase pregnancy rates by improving implantation rates.
  • 86. Indications for Assisted Hatching Older Age > 38 yrs Elevated FSH Egg quantity and quality factor Embryo quality poor quality embryos (excessive fragmentation or slow rates of cell division) Zona pellucida thickness >17 mm Previous IVF failures Cryo-preserved Embryos Embryo generated from IVM
  • 87. Assisted Hatching : Methods The main methods currently in use for assisted hatching are: īƒ˜ Chemical īƒ˜ Mechanical īƒ˜ Laser – allows grater degree of control and precision
  • 88. Blastocyst Transfer The first IVF human pregnancy was achieved by blastocyst transfer. A blastocyst is an embryo that has developed in culture for at least five days after fertilization A blastocyst gives a better idea of the competence of an embryo and has a higher chance of implantation than a cleaved embryo.
  • 89. Blastocyst Transfer ī‚—Conventional Transfer – D2 or D3 : 4 – 8 Cell ī‚—Availability of more physiological culture media made extended culture possible ī‚—Sequential Media – Used here ī‚—Phase I Sequence –Mimics the nutrients found in the Fallopian tube ī‚—Phase II Sequence – Mimics the nutrients found in the receptive uterine cavity
  • 90. Blastocyst Transfer - Advantages 1. Embryo selection with highest developmental potential 2. Synchronization with endometrium 3. Minimize the embryo exposure to the hyperstimulated uterine environment 4. Reduced embryo expulsion 5. Assessment of true viability after complete genomic activation 6. Higher implantation – Reduced need of multiple embryo transfer 7. Increased ability to undergo cryopreservation 8. Ability to undertake cleavage stage embryo biopsy 9. Increased overall efficiency of IVF
  • 91. Indications of Blastocyt Transfer Repeated failure to achieve pregnancy following the transfer of good quality cleaved embryos To achieve pregnancy without the risk of multiple pregnancy. Patient who do not wish to have their spare embryos frozen for whatever reasons may be advised to have blastocyst transfer.
  • 92. Pre implantation genetic diagnosis (PGD) ī‚— PGD is a new technique which combines the recent advances in molecular genetics and ART. ī‚— PGD was first reported in 1990. ī‚— It enables diagnosis of a genetic disorder in an embryo before its implantation in the uterus. ī‚— PGD involves embryo biopsy and genetic analysis which can be performed on - oocyte /zygote – polar body biopsy - blastomere from cleavage stage embryo - trophectoderm biopsy from blastocysts.
  • 93. Pre implantation genetic diagnosis (PGD) ī‚—PGD can be used to detect various diseases like: ī‚Ą Sickle cell anemia ī‚Ą Tay-sachs disease ī‚Ą Haemophilic ī‚Ą Cystic fibrosis ī‚—Diagnostic techniques used in PGD are ī‚Ą PCR ī‚Ą FISH ī‚—Following PGD unaffected embryos are transferred back into the uterine cavity
  • 94. PGD: Indications PGD is recommended most frequently for : ī‚Ą Patient with unexplained infertility ī‚Ą Recurrent miscarriages ī‚Ą Unsuccessful IVF cycles ī‚Ą Advanced maternal age ī‚Ą Sever male factor infertility
  • 95. Cryopreservation īļCryopreservation has become an integral component of assisted reproductive technology īļThe slow-freeze and rapid-thaw method used to be the most common method in cryopreservation īļVitrification– Cryopreservation using high concentrations of cryoprotectants to solidify the cell in a glass state without formation of ice. īļCryopreservation techniques are being developed for â€ĸ Gametes (Sperm /Oocytes) â€ĸ Embryo â€ĸ Gonadal tissues (Ovarian tissue)
  • 96. Embryo Cryopreservation â€ĸ Aim of cryopreservation To remove as much of intracellular water as in compatible with life, before freezing, so as to reduce the extent of intracellular ice formation to point where it ceases to constitute threat to the viability of the cell. Freezing of embryos allows significant chance of pregnancy after single ovarian stimulation Assuming all embryo survive freeze/thaw process the patient can undergo 2 cycles of transfer in a typical retrieval cycle of 15 oocytes The pregnancy rates of Vitrification technique is promising
  • 97. Embryo Cryopreservation : Advantages Freezing all embryos for subsequent transfer may be advised for women who are at a high risk of developing severe ovarian hyperstimulation syndrome following ovarian stimulation for in-vitro fertilization (IVF) When embryo implantation may be compromised in cases such as the presence of endometrial polyps, poor endometrial development Difficulty encountered at fresh embryo transfer e.g. cervical stenosis Cryopreservation of embryos is very important to be incorporated in the egg donation programs. It is not always possible to synchronize the recipient’s cycle with that of the egg donor
  • 98. Ovarian Tissue Cryopreservation ī‚—One ovary is removed laparoscopically and ovarian cortex is isolated ī‚—Cortex is cut into strips – 10 mm long, 5 mm wide and 1 mm thickness ī‚—They are incubated in cryoprotectants and frozen using a programmable freezer ī‚—Ethylene glycol (EG) and Dimethyl sulfoxide (DMSO)are the best cryoprotectants ī‚—7% of follicles are lost during freezing & thawing
  • 99. Oocyte Cryopreservation ī‚—Less effective – Mature oocyte extremely fragile ī‚—Reasons- Large size, water content & Chromosomal arrangements ī‚—Live birth rate /frozen oocyte ~ 3-4%
  • 100. Cytoplasmic Transfer īƒ˜ Egg from women undergoing IVF + ooplasma of donor is fertilized with sperm and resulting embryo is transferred back īƒ˜The child will have 3 genetic parent
  • 101. Mild IVF In-vitro fertilization is a complex treatment for infertility that entails costly regimens for ovarian stimulation serious discomfort to patients by daily injections multiple pregnancies ovarian hyperstimulation syndrome (OHSS) This has led to the development of mild in vitro fertilization (IVF) Treatment protocol which includes ī‚Ą Mild stimulation protocol ī‚Ą Single embryo transfer i.e. usually blastocyst Bioactive therapeutic preparations may revolutionize IVF treatment in near future
  • 102. INTRA-CYTOPLASMIC MORPHOLOGICALLY SELECTED SPERM INJECTION (IMSI) īļIntroduction of ICSI revolutionized the treatment of male factor infertility. īļICSI involves the microinjection of a single sperm into an egg IMSI helps to select best sperms based on morphology to improve the success and is said to be more beneficial than ICSI in patients with Two previous IVF or ICSI failures Unexplained infertility Severe male factor infertility Better advantage in terms of higher pregnancy rate and lower miscarriage rates.
  • 103. INTRA-CYTOPLASMIC MORPHOLOGICALLY SELECTED SPERM INJECTION (IMSI) The IMSI method was first developed in 2004 by a team led by Benjamin Bartoov, in Israel. IMSI is, becoming the most efficient variant of micromanipulation-assisted fertilization. It helps in magnifying the image of the sperm 7,200 times, thereby allowing to pick the best looking morphologically healthier sperms. advanced version of ICSI having the magnification capacity of 16 times higher than ICSI.
  • 105. Spindle View ī‚—Each egg has mitotic spindle ī‚—Chromosome spindle can now be visualized, while actually injecting the eggs. ī‚—This would prevent egg damage, increase fertilization rates, increase embryo formation rates and improve embryo quality ī‚—Any abnormality of spindle has high risk for developing into embryos with chromosomal abnormalities may result in failed fertilization, poor embryo development, failed implantation or spontaneous abortion
  • 106. Embryoscope EmbryoScope is a novel embryo monitoring system for assessing embryo quality. Using Leica optics it provides continuous control and recording of embryo development and provides respiration rates of single embryos during development image acquisition of embryo development onset and duration of cell divisions In future Embryoscope may replace the classical microscope based methods for selecting embryos
  • 107. EMBRYOSCOPE : EMBRYO MONITORING SYSTEM
  • 108. Proteomics : Embryo Selection in IVF ī‚—Embryo is an active participant in the process of implantation ī‚—It secretes various proteins that can be detected in the culture medium ī‚—Mass spectrometry have made it possible to analyze extremely small amounts of biological secretions ī‚—The protein profile can be used to differentiate between good-quality and degenerating blastocysts ī‚—Specific proteins were found to be secreted in larger amounts by good-quality embryos (ie, platelet- activating factor, leptin, acrogranin, HLA-G)
  • 109. Computer Assisted Semen Analysis (CASA) ī‚—CASA refers to an automated system (hardware and software) to visualize and digitize successive images of sperm and it’s process. ī‚—Analyzes the information, and provide accurate, precise, and meaningful information on the kinematics of individual sperm cells (count, motility and morphology) ī‚—Provides fast, accurate and objectively repeatable results in a complete report. ī‚—Makes the assessment of semen quality more subjective and detailed.
  • 110. Why CASA ? ī‚—Sperm concentration and motility measurements are least reliable with current manual methods. ī‚—Manual semen analysis is associated with large inter-laboratory variation. ī‚—Impossible to compare sperm motility assessments of different laboratories. ī‚—More detailed description of sperm movements is not possible with manual method (only 4 categories).
  • 111. Key Feature of CASA ī‚—Calculate the spermatic Counts & Concentrations of a sample ī‚—Detailed results on Motility & Progressive Motility, velocities, motion characteristic ī‚—Morphology and morphometry ī‚—DNA fragmentation study
  • 112. ART Success Rates 30%-40% of women who start each cycle of treatment achieve clinical pregnancy. Success rates have gone up beyond 50% in last 5 yrs. It depends on: īƒ˜ Age īƒ˜ Cause of infertility īƒ˜ Response to ovarian stimulation īƒ˜ Semen quality īƒ˜ Appearance of embryo generated and transferred
  • 113. Arpit Test Tube Baby Centre Record of IVF cases in last 12 years ī‚Ą 3596 IVF cases ī‚Ą 1876 cilinical pregnancy ; Overall Success rate 52.18% ī‚Ą 54 ectopic pregnancies 2.87% ī‚Ą 221abortions 11.8% Take home baby rate 38.44%
  • 114. Conclusions Significant advances have been made in assisted reproductive technology since the birth of the first test tube baby Increasing number of women is experiencing infertility today than in the past decades. Third party reproduction has become an important therapeutic option and, at times, the only option for couples seeking fertility treatment. New trends in ART have revolutionised the reproductive medicine in last one decade These new technologies have also improved success rates in ART Milder ovarian stimulation regimens are gaining acceptance and will likely be more widely used in years to come. Improved access and affordability of ART is the demand of the developing nation

Editor's Notes

  1. Ovulation disorder. Ovulation can be seriously affected by: Abnormalities of the thyroid gland Overproduction of prolactin (a hormone leading to breast milk production) Excessive male hormone (androgens) Physical stress, psychological stress and extreme lifestyle changes Cervical factors Causes include the following: Inadequate or inhospitable cervical mucous Cervical narrowing or &amp;quot;stenosis&amp;quot; Infections of the cervix with common sexually transmitted diseases (chlamydia, gonorrhea, or trichomonas, as well as mycoplasma hominis and ureaplasma urealyticum) Immune attack of sperm or &amp;quot;sperm allergy&amp;quot; Pelvic and tubal factors, ¡ Scar tissue or &amp;quot;adhesions&amp;quot; ¡ Endometriosis ¡ Blocked, scarred, or distorted fallopian tubes ¡ Benign tumors (fibroids) of the uterus Uterine causes include: Thin or abnormal uterine lining Anatomic problems (polyps, uterine fibroids, abnormal shape of the uterus, septum or &amp;quot;dividing wall&amp;quot; within the uterus)
  2. Infertility being a Universal problem is widely faced with challenges. Tremendous scientific progress has been made in the field of ART
  3. What is assisted hatching? Once fertilization has occurred, rapid cell division, expansion, formation of a fluid-filled cavity, and rupture of the zona pellucida (a protein coat surrounding the egg and embryo) characterize embryo development. This process takes 5-6 days from the time of fertilization. Several factors seem to be involved in the efficiency with which hatching occurs, and hence implantation and pregnancy. Normally, expansion of the embryo together with the production of enzymes by the embryo causes the zona to open, releasing the embryo. This is called &amp;quot;hatching.&amp;quot; The embryonic cells then come in contact with the lining of the uterus, allowing implantation and pregnancy. There is a very specific period of time during which implantation can occur. If an embryo has not hatched during this period, implantation does not occur. &amp;quot;Assisted hatching&amp;quot; is a form of micromanipulation, which is done during an IVF cycle, and is performed three days after the egg retrieval. It involves holding an embryo with a pipette, and, under high magnification, using a fine needle filled with a hatching solution to dissolve a portion of the zona. The embryos are then returned to culture, and transferred to the patient&amp;apos;s uterus later on that day. Because there is now a hole in the zona, and the embryo is therefore more exposed to the environment, the patient is put on a four day regimen of antibiotics and steroids prior to the transfer, to reduce inflammation and the risk of bacterial infection of the embryo which may occur as a result of the embryo transfer.
  4. Who benefits from this procedure? There are several groups of patients who may benefit from assisted hatching. Patients whose embryos have &amp;quot;thick&amp;quot; zonas seem to have a lower incidence of hatching. Patients with elevated baseline FSH levels, patients who are over the age of 38, patients who have failed 1 or more IVF cycles, and patients whose embryos grow slowly or have significant fragmentation may also benefit from assisted hatching. What are the risks? The risks of this technique include, but are not limited to damage or destruction of some or all of the embryos. There has been no reported increased incidence of birth defects in children born as a result of this procedure; some centers, however, have reported an increase in the number of identical twins.
  5. Laser being the latest breakthrough in Assisted Hatching. The use of Laser allows a greater degree of control and more precision during assisted hatching. It is an attempt to boost pregnancy rates.
  6. Preliminary evidence shows that the longer embryos are kept out of the uterus there are chances that it will not be expelled. Studies shows that blood loss from the egg retrieval process causes uterine contractions in some women. If the uterus contracts too many times in rapid succession the embryos will be expelled. By waiting five days to return the embryos to the uterus the body has a chance to reabsorb this blood and the contractions are greatly diminished.
  7. The availability of cryopreservation technology has extended the scope of ART and made it more convenient for patients. Cryopreservation are for Sperm Embryo Oocytes Aim of cryopreservation To remove as much of intracellular water as in compatible with life, before freezing, so as to reduce the extent of intracellular ice formation to point where it ceases to constitute threat to the viability of the cell.
  8. The availability of cryopreservation technology has extended the scope of ART and made it more convenient for patients. Cryopreservation are for Sperm Embryo Oocytes Aim of cryopreservation To remove as much of intracellular water as in compatible with life, before freezing, so as to reduce the extent of intracellular ice formation to point where it ceases to constitute threat to the viability of the cell.
  9. Success rates are around 45% at the age of 34yrs, while there is a steep decline by 40 yrs of age and above