Transcript Screening of egg donors

THIRD PARTY REPRODUCTION
&
CURRENT CONCEPTS IN ART
Dr. Vandana Bansal
MS, D.Phil.(Gold Medalist), DGO, FCGP
Senior Gynaecologist & Obstetrician
Infertility & IVF Specialist
Arpit Test Tube Baby Centre
Jeevan Jyoti Hospital, Allahabad
From the holy city of Sangam; Allahabad
Introduction
• The process of reproduction has long fascinated man
kind particularly from scientific perspectives.
• The sole objective of any living organism is to procreate
i.e. to reproduce itself.
• With an average monthly fecundity rate of 20%, human
beings are not fertile mammals.
• 10-15% of couples has difficulties in conceiving and
seeks special fertility care at least once during their
reproductive life time.
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)
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
The overall incidence of infertility has
remained relatively unchanged for the
past 30 years (Speroff & Fritz, 2005).
Approximately half of all women who
receive fertility care achieve conception
leading to a live birth (Speroff & Fritz, 2005).
Treatment Options… Overcoming Infertility
Nearly 90% of all infertility cases, both male
and female factor, can be successfully treated.
Treatment options are:
 Ovulation Induction
 Medical & Surgical treatment of Male
 Laparoscopic & Hysteroscopic Surgery for Female
 Intrauterine Insemination (IUI)
 Assisted Reproductive Technology (ART)
 Third party Reproduction
Human Reproduction – Changed
• 25th July, 1978
• Louise Joy Brown
• World’s First Successful Test Tube Baby
Landmark Event in Reproductive Revolution
Science Proves Wonders
Third Party Reproduction
• 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.
• Ethical, moral, religious and legal concerns play a
significant role in these treatments
• 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 …third party
There is also an increasing incidence of
Premature Ovarian Failure & Diminished
Ovarian Reserve
 For these women to concieve the only way out is to
use donor eggs(third party)
 Aged women
 Oophrectomy cases
 Cancer ovary and operated or irradiated
 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 donation……third party
Some women have untreatable
uterine abnormality RKH,
endometrial TB, hystrectomy, etc
The only chance of these couples to
have babies is through ……..……
…………Third party reproduction
Indications for Third-party reproduction
Women without functional ovaries
• Advanced maternal age
• Surgical or natural menopause
• Premature ovarian failure
• Previous chemotherapy or radiotherapy
• Women born without functional ovaries
Women with functional ovaries
• Recurrent pregnancy loss
• Repetitive IVF failures/poor response
• Women without functioning uterus
• Uterus that is unsuitable for pregnancy such as extensive fibroids, adenomyosis, or
Asherman’s
• Women with a serious medical condition that increases significant morbidity, or
even mortality if pregnancy occurs
• Inheritable disorders (carriers of genetic diseases & chromosomal abnormalities)
Male & Female same sex couple
Types of Third Party Reproduction
Oocyte donation
Sperm Donation
Embryo Donation
Surrogacy
Traditional surrogacy
Gestational surrogacy
What is Oocyte Donation?
 Egg donation is the part of third party reproduction.
 Eggs are retrieved from a young woman ( < 33 yrs ) called the donor.
 These eggs are fertilized with the sperms of the recipient’s husband.
 Resultant embryo is transferred to the uterus of the recipient.
 Oocyte donation has been used for more than 20 years to help infertile
couples become pregnant through IVF
 The first pregnancy achieved with egg donation was reported
in 1984.
Oocyte Donation: Indications
Women without ovarian function:
• Advanced maternal age
• Surgical or natural menopause
• Premature ovarian failure
• Women born without functional ovaries
• Previous chemotherapy or radiotherapy
Women with ovarian function:
• Recurrent pregnancy loss
• Repetitive IVF failures/poor response
• Inheritable disorders
Male same sex couple
Treating Women of Advance
Reproductive Age
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Age > 40 - ovarian functions is reduced
Oocytes are of poorer quality
Ovulation is less likely
Corpus luteum may be deficient in
hormone
• Blastocyst hatching is reduced
Steps of Egg Donation
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Selection of Donor
Selection of Recipient
Appropriate Stimulation of donor
Successful fertilization
Proper synchronization of donor and
recipient
Endometrial preparation of recipient
Atraumatic Embryo transfer
Hormonal support of recipient
Finally, adequate management of
pregnancy
Psychological consultation for
oocyte donor recipients
 The decision to proceed with donated oocytes is
complex, and patients and their partners (if
applicable) may benefit from psychological
counseling
 clinician should strongly recommend psychological
counseling by a qualified mental health professional
 The assessment should include a clinical interview
and, where appropriate, psychological testing.
 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.
 Anonymous Donors:
Recruited and screened by the ART program or by a
private agency.
 Directed donors:
Generally recruited by the recipients, and screened by
agencies or centers
The donor is generally a close relative or friend
 IVF programs:
Women undergoing IVF may agree to donate their excess
eggs to infertile patients
SOURCE OF OOCYTE DONORS
• The demand for donor oocytes far outstrips the
supply of donors.
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Volunteers
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Known donors
Spare oocytes
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Sterilization patients
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Professional oocyte donors
Selection of Donors
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Donors should be over 21 and under 34 years old
Younger donors tend to provide better eggs
Previous pregnancies by the donor is an asset
Detailed personal medical and family history
Blood tests for: infectious diseases, hepatitis B and HIV
(AIDS)
• Screened for any X chromosome-linked genetic disorders
• Anonymity
Matching the Intended Parent to
an Oocyte Donor
 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
 Medical matching (Blood group)
 Compensated for their time & effort
 Compensation remains the same no matter how
many oocytes are retrieved
Screening of egg donors: phase 1
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Donor age between 21 and 34
Both ovaries present
Not overweight
Nonsmoker
Off hormonal contraception for >2 months
Not adopted
If donor meets above criteria, then proceed to
phase 2
Screening of egg donors: phase 2
• Review questionnaire:
• Eliminate those with serious functional or
cosmetic handicaps or unknown family
background
• Eliminate those with high-risk behaviour for STDs
• If OK: evaluate basal FSH, LH, and estradiol
• If OK: review psychological evaluation
• If OK: donor should come to clinic for phase 3
Screening of egg donors: phase 3
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Physical examination
Cervical cultures
Gonorrhea
Mycoplasma (ureaplasma)
Herpes
Chlamydia
Blood tests
Syphilis serology
HIV-1 and HIV-2 (antigen and antibody tests)
Hepatitis B and C
Potential Risks to Egg Donors
•Inconvenience/ time commitment
•Discomfort associated with injections/blood draws
•Psychological risks - short and long term
Side effect of drugs:
- GnRH - hot flushes/ fatigue/ emotional liability
- Gonadotropins - bloating/ cramping
Potential Risks to Egg Donors
From retrieval:
• Pain
• Infection
• Bleeding
• Unexpected reaction to anaesthesia
• Ovarian hyperstimulation syndrome
• Sterility/Infertility from egg retrieval
• Unknown risk of ovarian cancer
SELECTION OF RECIPIENTS
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Should have an in-date cervical smear
Immunity to Rubella
Normal hemoglobin, blood group
Blood sugar level if above 40 years
Recipient and her partner should be Negative
for HIV I&II, Hepatitis B&C
Screening of egg recipients
Test/consultation
When needed
Hysterosalpingogram, saline
hysterosonography or
hysteroscopy
Within 3 years
Pap smear
Within 1 year
Mammogram
Within 5 years if recipient is
between ages 35 and 40, within 2
year if she is 51 years or older
Fasting glucose level
Within 3 years if anyone in
recipient's immediate family or two
or more people among her
relatives have diabetes, if she is
obese, or if she has had diabetes
while pregnant
Screening of egg recipients Cont..
Electrocardiogram
Within the year if recipient is aged 40
years or more
Total cholesterol level
Within the year if a parent or sibling of the
recipient has/ had a total >240 mg/dl, if
members of her family developed
premature (<55 years) cardiovascular
disease, if she has diabetes, or if she
smokes
Fecal occult blood screening
Within the year if the recipient is aged >50
years, or has/ had first-degree relatives
with colorectal cancer, or has had
endometrial, ovarian, or breast cancer
herself, or has had inflammatory bowel
disease, adenomatous polyps,
or
colorectal cancer herself, or has family
members with polyposis coli or cancer
family syndrome
Screening of egg recipients
Cont..
Preconceptual counseling
If recipient is age 35 years or
more, with an obstetrician, to
review risks of pregnancy
General medical screening
If recipient is age 45 years or
more, or gets short of breath, has
a heart murmur, or has an
abnormal electrocardiogram, a
high total cholesterol, or blood in
her stools
Psychological counseling
Recommended for all, but not
required
COUNSELLING OF DONORS
AND RECIPIENTS
All patients and their partners require a
detailed explanation of the procedures
involved in egg donation and counseling on
the moral, ethical and legal implications.
• Implications counseling
• Support counseling
• Therapeutic counseling
Methods And Protocols for Oocyte
Donation
• Egg donation consists of undergoing an IVF
Cycle up to the point of egg retrieval in
Donor.
• In Vitro fertilization with embryo formation.
• Fresh / Frozen - Embryo Transfer.
• Cyclic / Acyclic - Recipient with or without
ovarian function.
Egg Donation Treatment Sequence
Actual treatment is individualized
Protocols for Oocyte Donation
Fresh embryo transfer
• Careful synchronization of the donor and
recipient cycle.
• While donor undergoes super ovulation and
egg retrieval.
• Recipient receives the hormonal therapy to
prepare the endometrium for implantation.
Protocols for Oocyte Donation
• Markers of adequate endometrial development.
1. Serum Estradiol level
2. Endometrial Thickness (USG)
3. Late Luteal phase endometrial biopsy in
a test cycle.
• Egg sharing.
ADAVANTAGE OF FROZEN
EMBRYO TRANSFER.
• To overcome Endometrial Asynchrony
• To maintain Anonymity
• For embryo storage while donor has her blood
re-tested for HIV.
PROTOCOL FOR OOCYTE
DONATION
(in cyclic women)
• Synchronize the donor and recipient cycle by
– Norethisterone or Giving GnRH Agonist
• When both donor and recipient are down regulated
– Recipient starts Estrogen and donor starts ovarian
stimulation 5-6 days later.
• Progesterone started to recipient on the day of ovum
pickup of donor.
• Resulting embryos are transferred 3-5 days later or
cryopreserved
Schematic Diagram of an Oocyte
Donor Stimulation Protocol
Alternative protocols using GnRH antagonist can also be used
Schematic Diagram of a Recipient
Protocol.
•If the pregnancy test is positive, recipients are asked to continue the estrogen and
progesterone replacement until 10 weeks of gestation.
•If the pregnancy test is negative, patient can stop the hormonal replacement. E –
estrogen; P –progesterone.
Endometrial Receptivity
 Endometrial receptivity is the window of time when the uterine
environment is conductive to embryo acceptance and subsequent
implantation
 Endometrial receptivity can be accessed by
 Trans vaginal USG
 Colour Doppler
 Recently using 3D/4D USG
 Parameters for assessing endometrial receptivity:
 endometrial thickness (>7 - <14 mm)
 endometrial pattern (triple-line pattern)
 endometrial and subendometrial blood flow (within Zone 3 )
Window of Receptivity
• The condition of uterus becomes optimal for implantation for
a brief period during leuteal phase known as Window of
receptivity
• Short - last for 4 days (Day 20-24 of the menstrual cycle)
– +6 to 10 (Bergh and Navot 1992)
– +3.5 (Rogers 1989)
– +5 to 7 (Psychoyochos 1993)
Post ovulatory
Days
• During this period endometrium undergoes important
changes that makes it receptive to the implanting embryo
• Key factor in implantation is the synchrony between embryo
development & endometrial receptivity
STEROID REPLACEMENT AFTER
EMBRYO TRANSFER
(Estradiol Valurate)
• Estrogen dose is increased.
• Progesterone is started from the day of ovum pick up
in donor.
• Continue till pregnancy test is if positive.
• Increase progynova (Estrogen) to 8mg/day orally.
• Continue Estrogen and Progesterone until luteal
placental shift occurs i.e. upto 10-12 weeks of
pregnancy.
Luteal Phase Support
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Vaginal progestin Pressaries
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100 BD- if CC/FSH/HMG cycle
200 TDS- if GnRHa+HMG/FSH
Oral – Dehydrogestone 10 mg BD
 HCG 2000-2500 IU IM day 3
 Progesterone – 50-100 mg IM
Rationale and Indications
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• COH results in abnormal endometrial Development
• High level of estrogen seen in COH may cause premature luteolysis
• Pituitary down regulation with GnRHa is detrimental to luteal
phase
• Ovarian aspiration disrupts granulosa cells
• Important to synchronise embryo and endometrium for successful
implantation
Concerns & Complications
• Ethical, legal, religious & social issues
• Relationship between biological & social parents, &
safeguarding of the interests of the off spring, may be resolved
by specific legislation pertaining to each country
• Adequate study of the health risks of oocyte extraction,
including long-term risks
• Medical costs for adverse effects caused by the procedure
• True informed consent from women who provide oocytes
• Exploitation of poor women
• No meaningful oversight
Pregnancy Rates with Egg Donation
Depends on:
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Age of the Donor & Recipient
Cause of the couple's infertility
Quality & Developmental stage and number of embryos transferred
Endometrial Receptivity
Synchronization of the Embryo & Endometrium
Average live-birth rate per fresh embryo transfer is 55.1% (CDC , 2009)
The major risk for egg-donor programs is multiple gestations- 39.9%
(CDC, 2009)
Legal Issues
• Egg donation raises questions regarding all four of the basic
principles of medical ethics: autonomy, justice, beneficence,
and non-maleficence.
• Infertility specialists must consider these conflicts of interest.
• Egg donation is regulated and / or prohibited in many
countries.
• The egg recipient and the father of the child are the legal
parents.
• Most egg donors express a strong desire not to be identified by
the children.
• Should donor identity be revealed to egg donation child once
he/she reaches the age of 18 years??
Sperm Donation
SPERM BANKS
Sperm Donation
• Artificial insemination using donor sperm has been practiced for over a
century.
• The first published reports about the practice were in 1945.
• Over the past 10 years, the utilization of donor sperm has decreased due to
use of ICSI
• Since the late 1980s, with the emergence of AIDS artificial donor
insemination has been performed exclusively with frozen and quarantined
sperm.
• Current FDA and ASRM guidelines recommend that sperm be quarantined
for at least six months before being released for use
• 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
 Severe abnormalities in the semen Parameters
 Azoospermia : congenital or acquired.
 Obstructive azoospermia
 Non-obstructive azoospermia
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Severe oligospermia
Seminal fluid abnormalities
Single woman desiring pregnancy
Lesbians
DI is also indicated if the
 male has ejaculatory dysfunction
 male has significant genetic defect
 female is Rh-sensitized and the male partner is Rh-positive.
Psychological Consultation for
Recipients
 The decision to proceed with donor
insemination is complex , may benefit from
psychological counseling
 The clinician should strongly recommend
psychological counseling by a qualified
mental health professional
 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
• 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.
• The donor should be of legal age and, ideally, less than 40
years of age.
• Selection of donors with established fertility is desirable but
not required.
• Psychological evaluation and counseling
• The potential impact of the relationship between the donor and
recipient should be explored.
• 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
– More than one sample be examined (each after a 2- to 5-day abstinence
interval)
– The sample should be examined within 1 to 2 hours
– The minimum criteria for normal semen quality can be applied
2. Genetic evaluation
– Genetic screening for heritable diseases should be performed
– Testing for cystic fibrosis carrier status
3. Medical history
– Donors should be healthy and give no history to suggest hereditary disease.
– Complete personal and sexual history to exclude high risk for HIV, STIs, or
other infections
4. Physical examination
– Before acceptance, and every 6 months while remaining an active donor,
donors should undergo a complete physical examination
Choosing Donor Characteristics
• There are several methods for matching the male
partner with the donor.
• The couple should be encouraged to list the
characteristics that they desire in a prospective donor
– Race and/or ethnic group, height, body build, complexion,
eye color, and hair color and texture.
• Consideration should be given to blood type and Rh
factor, particularly for Rh-negative recipients.
The Insemination Procedure &
Pregnancy Rates
 Insemination may be timed based on a woman’s natural
cycle or in conjunction with an ovulation induction cycle
 It should occur close to the time of ovulation.
 The pregnancy rates depend on many factors
Age of the female recipient
Presence of other female fertility factors such as
endometriosis, tubal disease, or ovulatory dysfunction
 The monthly chance of pregnancy ranges from 8% to
15%.
 The risk of birth defects is no different than natural
conception and is in the range of 2% to 4%.
EMBRYO DONATIONS
EMBRYO DONATION
• In the current clinical practice of ART, more embryos
than can be transferred safely at one time commonly
are generated
• These embryos may be cryopreserved for later
transfer
• 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
• Embryo donation is a form of third party reproduction.
• 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
• Indications for embryo donation include
– Untreatable infertility that involves both
partners
– Untreatable infertility in a single woman
– Recurrent pregnancy loss thought to be
related to embryonic factors
– Genetic disorders affecting one or both
partners.
Medical and Psychological
Screening of Recipient Couple
• The process of embryo donation requires that
the recipient couple undergo the appropriate
medical and psychological screening
recommended for all gamete donor cycles.
• 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
• Pregnancy following embryo donation depends on:
– Age
– Whether it is fresh or frozen embryo transfer
– The quality & number of the embryos transferred
– Endometrial Receptivity
– Synchronization of the Embryo & Endometrium
Ethical and Legal Considerations
• Embryo donation is a controversial process from both an
ethical as well as a legal standpoint
• Child born to the couple will have no genetic link with them
• 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
• The practice of renting a womb and getting a child is like
outsourcing pregnancy
• 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 )
• Surrogacy may be defined as a method of reproduction
whereby a woman agrees to become pregnant and deliver a
child for a contracted party
• It is both a medically and emotionally complex process that
requires careful evaluation
History
 The practice of surrogacy first got momentum in
America.
 Attorney Noel Keane is generally recognized as the
architect of the legal idea of surrogate
motherhood.
 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
 Absence of uterus
 Congenital
 Hysterectomy
 Very small uterus/Non functional Uterus
 Congenital(t shaped & hypoplastic ut)
 Acquired (TB)
 Woman not able to carry pregnancy
 Danger to the life of the Intended Mother (severe heart, kidney or
respiratory disease, unstable diabetes, or severe high blood pressure)
 Genetic diseases
 Recurrent abortion
 Recurrent IVF faliure
 Single father
 Gay couples.
Types of Surrogacy
 Traditional surrogacy: Straight or partial surrogacy
Surrogate mother inseminated
She is biological parent and gestational mother
Baby’s genetic parents are surrogate mother and
commissioning father
Commissioning mother has to accept child her male partner
fathered with another woman
 Gestational surrogacy: full or host surrogacy
Gestational embryo (genetic material) of the couple
Surrogate mother not genetically related to foetus
IVF
Types of Surrogacy
• Altruistic surrogacy:
– Surrogate receives no financial reward for her pregnancy
– all expenses such as medical expenses, maternity clothing,
and other related expenses related to the pregnancy and
birth are paid by the intended parents
• Commercial surrogacy:
– surrogates are paid for carrying a child to maturity in her
womb
– This is legal in several countries including in India
The baby born by surrogacy may
be the biological child of:
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Both parents
Mother & sperm donor
Surrogate mother & IF (intended father)
Neither parent
Steps in Surrogacy
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Proper patient selection
Source of surrogate (ART bank)
Proper selection & screening of the surrogate
Intensive counselling – the key factor
Synchronizing the cycles of the surrogate and
the genetic mother
Proper controlled ovarian stimulation and IVF
technique
Preparing the surrogate
Window period for embryo transfer
Taking care of the legalities and financial
contracts
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
 A review of all alternative treatment options
 The practical difficulty and cost of treatment by gestational
surrogacy
 The medical and psychological risks of surrogacy
 Potential psychological risk to the child
 The chances of having a multiple pregnancy
 The degree of involvement that the host may wish to have with
the child
 The possibility that the host may wish to retain the child after
birth
 The possibility that a child may be born with a handicap
 The importance of obtaining legal advice
Selection of Surrogate
Improper selection of the surrogate can create
problems at any stage of the procedure
ART – 2010 has defined the criterias for
screening a surrogate
Indian guidelines for ART ( pending for LAW)
Surrogacy, allowed in India
Counseling for the surrogate
 The full implications of undergoing treatment by IVF
surrogacy
 The possibility of multiple pregnancy
 The possibility of her family and friends being against her
having treatment
 The medical risks associated with pregnancy and delivery
 The implications of guilt on both sides if the host should
spontaneously abort a pregnancy
 The possible effect on her own children of acting as a surrogate
 The possibility that the host may fell a sense of bereavement
when she gives the baby to the commissioning couple
Screening for the surrogate
A physical examination and pap smear
Infective disease testing
Hysteroscopy
A mock cycle
Psyclogical testing and evaluation
Agreement /Contract
 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.
 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
 Surrogacy in India is of low cost and the laws are
flexible.
 Commercial surrogacy is legalized in India since 2002
but there is an immediate need of some strong
legislations
 In 2008, the Supreme Court of India in the Manji's case
(Japanese Baby) has held that commercial surrogacy is
permitted in India.
 There is an upcoming Assisted Reproductive
Technology Bill, aiming to regulate the surrogacy
business.
International Surrogacy
 There is growing evidence that surrogacy in India is
gaining international confidence .
 Framing international guidelines on the practice of
surrogacy is the challenge of the day.
 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
 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
–
–
–
–
Ongoing psychologic counselling costs
Pregnancy complications cost
Maternal complications
Fetal complications as multiple pregnancy/ selective fetal
reduction
– Genetic amniocentesis if required
– Medical complications
Problems in Surrogacy
 When problems arise in surrogacy it is usually because
of a breakdown in communication or counseling
 Issues that need to be comprehensively addressed are
•
•
•
•
•
•
Medical process
Realistic expectations for all parties
Signing the contract
Potential complications
Financial and legal matters
Establishment of parameters of acceptable conduct
by the parties.
Practical Problems
What if
The surrogate is not traceable or refuses to hand over the
child?
Anomalous baby born ?
Abortion or preterm delivery?
Contracts HIV during pregnancy?
Couple does not come to take the child?
Couples divorce ?
Death of comisioning parents ?
Country of commisiong parents does not allow baby to enter
the country ?
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
Death of the surrogate?
Realistic expectations for all Parties
1.
2.
3.
4.
5.
Transparency of the procedure
Trust
Commitment of all the people involved
Respect for one another
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
 The options available through Third party reproduction provides
many couples the opportunity to make their dream of parenthood
a reality.
 The comprehensive nature of screening & counseling of
intended parents & their donors or surrogates ensures that the
process meets the needs of all involved
 As Third party reproduction is more widely used continued
attention to personal, moral and ethical issues should be given.
 The ultimate goal of physicians & attorneys specialising in
reproductive law is to enable this process to move forward as
smoothly as possible & bring joy & satisfaction to all parties
involved in ensuring conception & delivery of healthy child.
NEW TRENDS
IN ASSISTED REPRODUCTION
New Trends in Assisted Reproduction
 In vitro egg maturation (IVM)
 Assisted Hatching
 Cytoplasmic transfer
 Mild IVF
 Preimplantation Genetic Diagnosis (PGD)
 Frozen Embryo Transfer (FET) / Cryopreservation
 Intra-Cytoplasmic Morphologically Selected Sperm Injection
(IMSI)
 Embryoscope
 Computer Assisted Semen Analysis (CASA)
IN VITRO MATURATION - IVM
 Mild and safe IVF
 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:
 Chemical
 Mechanical
 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
• Conventional Transfer – D2 or D3 : 4 – 8 Cell
• Availability of more physiological culture media
made extended culture possible
• Sequential Media – Used here
• Phase I Sequence –Mimics the nutrients found in
the Fallopian tube
• Phase II Sequence – Mimics the nutrients found in
the receptive uterine cavity
Blastocyst Transfer - Advantages
1.
2.
3.
4.
5.
6.
7.
8.
9.
Embryo selection with highest developmental potential
Synchronization with endometrium
Minimize the embryo exposure to the hyperstimulated
uterine environment
Reduced embryo expulsion
Assessment of true viability after complete genomic
activation
Higher implantation – Reduced need of multiple embryo
transfer
Increased ability to undergo cryopreservation
Ability to undertake cleavage stage embryo biopsy
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)
• PGD is a new technique which combines the recent
advances in molecular genetics and ART.
• PGD was first reported in 1990.
• It enables diagnosis of a genetic disorder in an embryo before its
implantation in the uterus.
• 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)
• PGD can be used to detect various diseases like:
–
–
–
–
Sickle cell anemia
Tay-sachs disease
Haemophilic
Cystic fibrosis
• Diagnostic techniques used in PGD are
– PCR
– FISH
• Following PGD unaffected embryos are transferred back into
the uterine cavity
PGD: Indications
PGD is recommended most frequently for :
–
–
–
–
–
Patient with unexplained infertility
Recurrent miscarriages
Unsuccessful IVF cycles
Advanced maternal age
Sever male factor infertility
Cryopreservation
Cryopreservation has become an integral component of
assisted reproductive technology
The slow-freeze and rapid-thaw method used to be the
most common method in cryopreservation
Vitrification– Cryopreservation using high concentrations of
cryoprotectants to solidify the cell in a glass state without
formation of ice.
Cryopreservation techniques are being developed for
• Gametes (Sperm /Oocytes)
• Embryo
• Gonadal tissues (Ovarian tissue)
Embryo Cryopreservation
• 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
• One ovary is removed laparoscopically and ovarian
cortex is isolated
• Cortex is cut into strips – 10 mm long, 5 mm wide and 1
mm thickness
• They are incubated in cryoprotectants and frozen using a
programmable freezer
• Ethylene glycol (EG) and Dimethyl sulfoxide
(DMSO)are the best cryoprotectants
• 7% of follicles are lost during freezing & thawing
Oocyte Cryopreservation
• Less effective – Mature oocyte extremely fragile
• Reasons- Large size, water content & Chromosomal
arrangements
• Live birth rate /frozen oocyte ~ 3-4%
Cytoplasmic Transfer

Egg from women undergoing IVF +
ooplasma of donor is fertilized with sperm
and resulting embryo is transferred back
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
 Mild stimulation protocol
 Single embryo transfer i.e. usually blastocyst
Bioactive therapeutic preparations may
revolutionize IVF treatment in near future
Intra-Cytoplasmic Morphologically
Selected Sperm Injection (IMSI)
Introduction of ICSI revolutionized the treatment of male
factor infertility.
ICSI 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
• Each egg has mitotic spindle
• Chromosome spindle can now be visualized, while actually
injecting the eggs.
• This would prevent egg damage, increase fertilization
rates,
increase embryo formation rates and improve
embryo
quality
• 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
 Embryo is an active participant in the process of
implantation
 It secretes various proteins that can be detected in the
culture medium
 Mass spectrometry have made it possible to analyze
extremely small amounts of biological secretions
 The protein profile can be used to differentiate
between good-quality and degenerating blastocysts
 Specific proteins were found to be secreted in larger
amounts by good-quality embryos (ie, plateletactivating factor, leptin, acrogranin, HLA-G)
Computer Assisted Semen Analysis
(CASA)
 CASA refers to an automated system (hardware and
software) to visualize and digitize successive images of
sperm and it’s process.
 Analyzes the information, and provide accurate, precise,
and meaningful information on the kinematics of
individual sperm cells (count, motility and
morphology)
 Provides fast, accurate and objectively repeatable results
in a complete report.
 Makes the assessment of semen quality more subjective
and detailed.
Why CASA ?
• Sperm concentration and motility measurements are
least reliable with current manual methods.
• Manual semen analysis is associated with large interlaboratory variation.
• Impossible to compare sperm motility assessments of
different laboratories.
• More detailed description of sperm movements is not
possible with manual method (only 4 categories).
Key Feature of CASA
• Calculate the spermatic Counts & Concentrations of
a sample
• Detailed results on Motility & Progressive Motility,
velocities, motion characteristic
• Morphology and morphometry
• 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:





Age
Cause of infertility
Response to ovarian stimulation
Semen quality
Appearance of embryo generated and transferred
Arpit Test Tube Baby Centre
Record of IVF cases in last 12 years
– 3596 IVF cases
– 1876 cilinical pregnancy ;
Overall Success rate 52.18%
– 54 ectopic pregnancies 2.87%
– 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