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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
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


• 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

•   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.
  1    Volunteers
  2    Known donors
  3    Spare oocytes
  4    Sterilization patients
  5    Professional oocyte donors
            Selection of Donors


• 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


•   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

•   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




•   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   Within 3 years
hysterosonography or
hysteroscopy


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)                       Post ovulatory
    – +5 to 7 (Psychoyochos 1993)              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

   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
     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:
    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
   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:


•   Both parents
•   Mother & sperm donor
•   Surrogate mother & IF (intended father)
•   Neither parent
             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
                   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.   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
 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.    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)

• 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, platelet-
  activating 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 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).
             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

				
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