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Third Party Reproduction
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
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.
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
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).
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 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
8. Human Reproduction – Changed
25th
July, 1978
Louise Joy Brown
World’s First Successful Test Tube Baby
Landmark Event in Reproductive Revolution
Science Proves Wonders
9. 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.
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 …third party
11. 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)
12. 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
13. Some women have untreatable uterine
abnormality RKH, endometrial TB,
hystrectomy, etc
14. The only chance of these couples to
have babies is through ……..……
……………third party reproduction
15. 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
Male & Female same sex couple
16. Types of Third Party Reproduction
Oocyte donation
Sperm Donation
Embryo Donation
Surrogacy
Traditional surrogacy
Gestational surrogacy
17. What is Oocyte Donation?
Egg donation is the part of third party reproduction.Egg donation is the part of third party reproduction.
Eggs are retrieved from a young woman ( < 33 yrs ) calledEggs are retrieved from a young woman ( < 33 yrs ) called
the donor.the donor.
These eggs are fertilized with the sperms of the recipient’sThese eggs are fertilized with the sperms of the recipient’s
husband.husband.
Resultant embryo is transferred to the uterus of theResultant embryo is transferred to the uterus of the
recipient.recipient.
18. Oocyte Donation
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 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:
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
20. The Oocyte Donation Process
The recipient couple
Psychological issues
Medical Screening
Legal Issues
Ethical concerns
The donor
Donor recruitment
Donor Screening
Donor matching
21. 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
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.
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
25. Donors
IVF patients, willing to share their extra- oocytes
(OOCYTE SHARING PROGRAMME( COMMON )
Women with tubectomy, willing to be hyperstimulated
( MONETARY COMPENSATION)
Known donors include family members who come
forward to donate their oocytes ( FAMILY )
Professional donors, recruited after advertisement
(MONETARY COMPENSATION)
Volunteers , philanthropic enough to donate their oocytes
(RARE BUT MAY FIND SUCH)
26. Selection of Donors
Oocyte donation may be undertaken with known or anonymous
Psychological evaluation and counseling
Oocyte donors should be of legal age (21 - 34 years).
Donors less than 21 years of age should have psychological evaluation
and decision should be on an individual basis.
If a donor is over 34 yr, it should be revealed to recipient concerning
cytogenetic risks and pregnancy rates.
Proven fertility in the donor is desirable
The donor should undergo appropriate genetic evaluation
If sharing of oocytes is contemplated, informed consent must be
obtained
27. Donor Screening
Suggested medical ,personal, family (genetic) &
reproductive history
Complete blood count with platelets
Blood type
Hepatitis screen
VDRL
HIV-1, HIV- 2
Cervical cultures for gonorrhoea and Chlamydia
Pap smear
Transvaginal ultrasound of pelvis
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
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 & other diseases)
Compensated for their time & effort
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
The synchronization of cycles in the donor
and recipient is extremely important to the
success of the oocyte donation.
The treatment cycles of the oocyte donor
and the cycling recipients involve pituitary
suppression by GnRH agonist
Alternative protocols using GnRH
antagonist can also be used.
32. Schematic Diagram of an Oocyte Donor
Stimulation Protocol
Alternative protocols using GnRH antagonist can also be used
33. Ovum Pick Up
Approximately 36 hours after the
hCG injection
Short G/A anesthesia
TVS aspiration is done with needle
connected to aspiration pump
Identification of oocytes is done in Lab
simultaneously
Earlier laparoscopic aspiration was done
Antibiotic cover is given for 5 days
Patient can go home after 3-4 hours
34. Protocol for Recipient
The uterus is prepared using hormones (estrogen and
progesterone) to mimic the natural menstrual cycle
GnRHa is used to suppress the pituitary gland to prevent the
patient from ovulating during the preparation of the uterus
Once the pituitary gland is suppressed, exogenous estrogen is
given & in turn it thickens the uterine lining
Pills, Patches, or even Injections
Progesterone started once endometrium is >8mm & on the
day of oocyte retrieval in donor
Vaginal suppository or Gel or as Injections
The no. of days progesterone is given before the transfer must
match the stage of embryo development
35. 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.
36. Endometrial Receptivity
Endometrial receptivity is the window of time when the uterine
environment is conductive to embryo acceptance and subsequent
implantation
Timely expression of a number of complex molecules like hormones,
cytokines & growth factors, and their crosstalk play a crucial role in
preparing receptive endometrium
Endometrial histology is influenced by estradiol & progesterone and
their synchronization is essential for implantation window
Parameters for assessing endometrial receptivity include:
endometrial thickness (>7 - <14 mm)
endometrial pattern (triple-line pattern)
endometrial and subendometrial blood flow (within Zone 3 )
37. 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)
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
Post ovulatory
Days
39. Luteal Phase Support
Vaginal progestin Pressaries
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
• 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
40. 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
41. Pregnancy Rates with Egg
Donation
Depends on:
Age of the Donor & Recipient
Cause of the couple's infertility
Quality & Developmental stage and number of embryos
transferred
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)
42. 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??
45. 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.
46. 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
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.
47. 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
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
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.
50. 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
51. 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.
52. 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%.
54. 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.
55. 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.
56. 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.
57. 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.
58. The Embryo Donation &
Pregnancy Rates
Pregnancy following embryo donation
depends on:
Whether it is fresh or frozen embryo transfer
The quality of the embryos
The age of the egg donor & recepient
And the number of embryos transferred
59. 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
61. 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
62. 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.
63. 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.
64. 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
65. 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
66. The baby born by surrogacy may
be the biological child of:
Both parents
Mother & sperm donor
Surrogate mother & IF (intended father)
Neither parent
67. Steps in Surrogacy
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
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
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
70. 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
71. 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
72. Screening for the surrogate
A physical examination and pap smear
Infective disease testing
Hysteroscopy
A mock cycle
Psyclogical testing and evaluation
73. 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.
74. 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.
75. 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.
76. 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
77. 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.
78. 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?
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
Third party parenting represents a significant treatment in
reproductive medicine
Extremely favorable success rates can be achieved
As technology grows and more awareness is generated, the
ability to offer parenthood to more people also increases
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.
Ethical guidelines and appropriate legislations with
contributions from the medical and scientific community
are gradually being established worldwide.
83. 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)
84. 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.
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:
Chemical
Mechanical
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
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
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)
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.
93. 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
94. PGD: Indications
PGD is recommended most frequently for :
Patient with unexplained infertility
Recurrent miscarriages
Unsuccessful IVF cycles
Advanced maternal age
Sever male factor infertility
95. 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)
96. 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
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
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
100. 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
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
Mild stimulation protocol
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)
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.
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
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
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
108. 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, platelet-
activating factor, leptin, acrogranin, HLA-G)
109. 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.
110. Why CASA ?
Sperm concentration and motility measurements
are least reliable with current manual methods.
Manual semen analysis is associated with large
inter-laboratory 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).
111. 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
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:
Age
Cause of infertility
Response to ovarian stimulation
Semen quality
Appearance of embryo generated and transferred
113. 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%
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
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 &quot;stenosis&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 &quot;sperm allergy&quot;
Pelvic and tubal factors,
· Scar tissue or &quot;adhesions&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 &quot;dividing wall&quot; within the uterus)
Infertility being a Universal problem is widely faced with challenges. Tremendous scientific progress has been made in the field of ART
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 &quot;hatching.&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.
&quot;Assisted hatching&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&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.
Who benefits from this procedure?
There are several groups of patients who may benefit from assisted hatching. Patients whose embryos have &quot;thick&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.
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.
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.
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.
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.
Success rates are around 45% at the age of 34yrs, while there is a steep decline by 40 yrs of age and above