THIRD PARTY THIRD PARTY REPRODUCTIONREPRODUCTION

&

CURRENT CONCEPTS IN ART

Dr. Vandana BansalMS, D.Phil.(Gold Medalist), DGO, FCGP

Senior Gynaecologist & ObstetricianInfertility & IVF Specialist

Arpit Test Tube Baby CentreJeevan 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 year10% remain infertile by end of 2nd year

Incidence - 10% to 15%

InfertilityPrevalence 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 conceptionleading 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 womenOophrectomy casesCancer ovary and operated or irradiatedPremature 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

•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

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, salinehysterosonography orhysteroscopy

Within 3 years

Pap smear Within 1 year

Mammogram Within 5 years if recipient isbetween ages 35 and 40, within 2year if she is 51 years or older

Fasting glucose level Within 3 years if anyone inrecipient's immediate family or twoor more people among herrelatives have diabetes, if she isobese, or if she has had diabeteswhile pregnant

Screening of egg recipients Cont..

Electrocardiogram Within the year if recipient is aged 40years or more

Total cholesterol level Within the year if a parent or sibling of therecipient has/ had a total >240 mg/dl, ifmembers of her family developedpremature (<55 years) cardiovasculardisease, if she has diabetes, or if shesmokes

Fecal occult blood screening Within the year if the recipient is aged >50years, or has/ had first-degree relativeswith colorectal cancer, or has hadendometrial, ovarian, or breast cancerherself, or has had inflammatory boweldisease, adenomatous polyps, orcolorectal cancer herself, or has familymembers with polyposis coli or cancerfamily syndrome

Screening of egg recipients Cont..

Preconceptual counseling If recipient is age 35 years ormore, with an obstetrician, toreview risks of pregnancy

General medical screening If recipient is age 45 years ormore, or gets short of breath, hasa heart murmur, or has anabnormal electrocardiogram, ahigh total cholesterol, or blood inher stools

Psychological counseling Recommended for all, but notrequired

COUNSELLING OF DONORS AND RECIPIENTS

All patients and their partners require a detailed explanation of the procedures involved in egg donation and counseling on the moral, ethical and legal implications.

• Implications counseling

• Support counseling

• Therapeutic counseling

Methods And Protocols for Oocyte Donation

• Egg donation consists of undergoing an IVF Cycle up to the point of egg retrieval in Donor.

• In Vitro fertilization with embryo formation.• Fresh / Frozen - Embryo Transfer.• Cyclic / Acyclic - Recipient with or without

ovarian function.

Egg Donation Treatment Sequence

Actual treatment is individualized

Protocols for Oocyte Donation

Fresh embryo transfer• Careful synchronization of the donor and

recipient cycle.• While donor undergoes super ovulation and

egg retrieval.• Recipient receives the hormonal therapy to

prepare the endometrium for implantation.

Protocols for Oocyte Donation

• Markers of adequate endometrial development.

1. Serum Estradiol level

2. Endometrial Thickness (USG)

3. Late Luteal phase endometrial biopsy in a test cycle.

• Egg sharing.

ADAVANTAGE OF FROZEN EMBRYO TRANSFER.

• To overcome Endometrial Asynchrony • To maintain Anonymity• For embryo storage while donor has her blood

re-tested for HIV.

PROTOCOL FOR OOCYTE DONATION

(in cyclic women)

• Synchronize the donor and recipient cycle by – Norethisterone or Giving GnRH Agonist

• When both donor and recipient are down regulated

– Recipient starts Estrogen and donor starts ovarian stimulation 5-6 days later.

• Progesterone started to recipient on the day of ovum pickup of donor.

• Resulting embryos are transferred 3-5 days later or cryopreserved

Schematic Diagram of an Oocyte Donor Stimulation Protocol

Alternative protocols using GnRH antagonist can also be used

Schematic Diagram of a Recipient Protocol.

•If the pregnancy test is positive, recipients are asked to continue the estrogen and progesterone replacement until 10 weeks of gestation. •If the pregnancy test is negative, patient can stop the hormonal replacement. E – estrogen; P –progesterone.

Endometrial Receptivity

Endometrial receptivity is the window of time when the uterine environment is conductive to embryo acceptance and subsequent implantation

Endometrial receptivity can be accessed by

Trans vaginal USG Colour Doppler Recently using 3D/4D USG

Parameters for assessing endometrial receptivity:

endometrial thickness (>7 - <14 mm)

endometrial pattern (triple-line pattern)

endometrial and subendometrial blood flow (within Zone 3 )

Window of Receptivity

• The condition of uterus becomes optimal for implantation for a brief period during leuteal phase known as Window of receptivity

• Short - last for 4 days (Day 20-24 of the menstrual cycle)– +6 to 10 (Bergh and Navot 1992)

– +3.5 (Rogers 1989)

– +5 to 7 (Psychoyochos 1993)

• 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

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 IMRationale 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 & RecipientCause of the couple's infertility Quality & Developmental stage and number of embryos transferredEndometrial ReceptivitySynchronization of the Embryo & EndometriumAverage 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 inSevere abnormalities in the semen Parameters Azoospermia : congenital or acquired.

Obstructive azoospermia Non-obstructive azoospermia

Severe oligospermia Seminal fluid abnormalitiesSingle woman desiring pregnancyLesbians 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 counselinga. 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 dysfunctionThe 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 fatherGay couples.

Types of Surrogacy

Traditional surrogacy: Straight or partial surrogacySurrogate mother inseminatedShe is biological parent and gestational mother Baby’s genetic parents are surrogate mother and

commissioning fatherCommissioning mother has to accept child her male partner

fathered with another woman

Gestational surrogacy: full or host surrogacyGestational embryo (genetic material) of the coupleSurrogate mother not genetically related to foetusIVF

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 treatmentThe medical risks associated with pregnancy and deliveryThe implications of guilt on both sides if the host should

spontaneously abort a pregnancyThe possible effect on her own children of acting as a surrogateThe 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 smearInfective disease testingHysteroscopy A mock cyclePsyclogical 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 ifThe 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 ReproductionConclusion

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 ReproductionIn 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 IVFIVM 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 pellucidaDefective Hatching may lead to failed implantationAssisted Hatching is a micromanipulative procedure involves slicing, dissolving or making a small opening in zona pellucidaHelps to increase pregnancy rates by improving implantation rates.

Indications for Assisted Hatching

Older Age > 38 yrsElevated FSHEgg quantity and quality factorEmbryo 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 potential2. Synchronization with endometrium3. Minimize the embryo exposure to the hyperstimulated

uterine environment4. Reduced embryo expulsion5. Assessment of true viability after complete genomic

activation6. Higher implantation – Reduced need of multiple embryo

transfer7. Increased ability to undergo cryopreservation8. Ability to undertake cleavage stage embryo biopsy9. 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 hyperstimulationsyndrome 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 developmentDifficulty encountered at fresh embryo transfer e.g. cervical stenosisCryopreservation 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 stimulationserious discomfort to patients by daily injectionsmultiple 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 eggIMSI 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 failuresUnexplained infertilitySevere male factor infertilityBetter 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

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%

Arpit Test Tube Baby Centre

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