art assisted reproductive technology dithawut khrutmuang md

ARTAssisted reproductive technology

Dithawut Khrutmuang MD.

Assisted reproductive technology

• All treatments or procedures which include the handling of human

oocytes or embryos, including in vitro fertilization, gamete

intrafallopian transfer, zygote intrsifallopian transfer, and such other

specific technologies as the Secretary may include in this definition.

1992 Fertility Clinic Success Rate and Certification Act

Assisted Reproductive Technology (ART)

• In vitro fertilization-embryo transfer (IVF-ET)/intracytoplasmic sperm injection

(ICSI)

• Gamete intrafallopian transfer (GIFT)/ Zygote intrafallopian transfer (ZIFT)

• Frozen embryo transfer (FET).

• ART may be recommended when other treatments (such as intrauterine

insemination) have not been successful or when there is severe male factor

infertility, severe endometriosis or tubal obstruction.2011 the American Society for Reproductive Medicine

Evaluation before ART

• General

• Before starting ART, each patient is evaluated to help maximize her chances for success

and a healthy pregnancy.

• Chronic medical conditions such as diabetes, hypertension and asthma should be well

controlled before attempting to conceive.

• Women planning an IVF cycle should optimize their weight. Obesity has been associated

with infertility, a reduced chance of success with IVF, and an increase in the risk of

miscarriage and preterm birth.

2011 the American Society for Reproductive Medicine

Ovarian reserve test

J Hum Reprod Sci. 2011 Sep-Dec; 4(3): 108–113.

Evaluation before ART

• Uterus

• The uterus is usually evaluated prior to an IVF. Three methods can be used: HSG, SIS or

hysteroscopy.

• Prior to IVF, a trial or “mock” transfer may be done. The purpose of this procedure is to

determine the length and direction of the uterus.

• Semen

• A semen analysis should be reviewed. Changes in sperm quality may occur over time

that could affect IVF success. 2011 the American Society for Reproductive Medicine

Prerequisite test before ART

• Female

HIV

Hepatitis B antigen

Hepatitis C antibody

VDRL/RPR

Pap smear

Blood group, Rh, and antibody screen

• Male

HIV

Hepatitis B antigen

Hepatitis C antibody

VDRL/RPR

Complex semen analysis, antisperm

antibodies, and strict morphology2011 the American Society for Reproductive Medicine

STRONGLY RECOMMENDED PRENATAL TESTS

• Female

• Rubella titer

Varicella titer

Hemoglobin electrophoresis

Cervical swab for Gonorrhea and

Chlamydia

• Male

• Hemoglobin electrophoresis


ART Cycle• Pre-stimulation treatment

• Ovarian stimulation with gonadotropins

• Monitoring follicle development

• Final oocytes maturation

• Transvaginal oocyte retrieval

• Insemination

• Embryo transfer

• Progesterone supplementation

• Pregnancy test Early pregnancy follow-up 2011 the American Society for Reproductive Medicine

Ovarian stimulation with gonadotropins

Santos M A et al. 2010;139:23-34

©2009 by Society for Reproduction and Fertility

Ovulation induction VS. Controlled ovarian hyperstimulation

Ovulation induction

• Use in anovulatory infertility.

• Restore physiologic of cyclic

ovarian function.

• Aim : Ovulation of single follicle

Controlled ovarian hyperstimulation

• Superovulation

• Stimulation of multiple follicular

development

• Aim : multiple follicular

development for ART


Controlled ovarian hyperstimulation

Long agonist Antagonist

Merck & Co., Inc

GnRH agonist / antagonist used to inhibit a premature LH surge

GnRH Agonists

• Gonadotropin releasing hormone (GnRH) is a hormone produced in the brain that indirectly stimulates ovarian function.

• Agonists of GnRH are synthetic forms of this hormone

• Mechanism Of Action• Agonists of GnRH initially stimulate the pituitary gland to release all the stored

gonadotropins (LH and FSH -the hormones that normally stimulate ovarian function). • Over the course of a week to 10 days, GnRH analogs suppress the production of any new LH

and FSH. This effect appears to prevent the ovaries from receiving mixed signals from the patient's own LH and FSH and from the medications that are administered to stimulate follicle development.

• The result for many patients is a more synchronized development of mature oocytes.


GnRH agonist protocol Route of administration

Days of cycle ( CD) Duration administration

Ultrashort NS / SC 2,3 – 4,5 3 days

Short NS / SC 2,3 until day of hCG 8 -12 days

Menstrual early cessation NS / SC 21 until menses 7 -12 days

Follicular early cessation NS / SC 21 until stimulate D6,7 13 -20 days

Long follicular NS / SC 2 until day of hCG 28 -35 days

Long follicular(depot) Depot 2 Once

Long luteal NS / SC 21 until day of hCG 21 -28 days

Long luteal(depot) Depot 21 Once

Ultralong NS / SC / Depot 2 or 21 8-12 weeks , depot 2-3 times

GnRH agonist protocol Advantasge Disadvantage

Ultrashort Patient’s comfort, Poor responders Low PR, Low oocyte qualityNo programming

Short Patient’s comfort, Poor responders Low PR, Low oocyte qualityNo programming

Menstrual early cessation Inconclusive Low E2 level, high cancel rate

Follicular early cessation Inconclusive Low E2 level, high cancel rate

Long follicular Good PR, High number oocytes, programming Long duration

Long follicular(depot) Patient’s comfort Too long duration of action

Long luteal Good PR , programming Long duration

Long luteal(depot) Patient’s comfort Too long duration of action

Ultralong Endometriosis Sideeffects due to estrogen deficiency

GNRH Antagonists

• Antagonists of GnRH are directly and immediately inhibit FSH and LH production.

• Ultrasound measurements of follicular growth are used to determine when to start these medicines.

• Mechanism of Action• GnRH antagonists bind to the receptor for gonoadotropin releasing hormone

on the pituitary, preventing the natural luteinizing hormone surge and ovulation.


GnRH antagonist protocols

• Complex heterodimeric glycoproteins• 2 non-covalent linked proteins:

α -subunit:β -subunit: unique, specific hormonal function

Gonadotropins ; use in ovarian stimulation

• Pregnant mare serum

• Pig pituitary gland extracts

• Human menopausal gonadotropin (hMG)

• Recombinant human gonadotropins

Exogenous gonadotropins

Corifollitropin alfa ;New long-acting gonadotropins

• A heterodimeric glycoproteins• Bind to receptor on the theca cells and granulosa cells (late follicular phase)• Main role:

• Stimulate androgen production from the theca cells• Triggering ovulation• Supporting the corpus luteum

• Indication:

• Hypogonadotropic hypogonadism

• Profound pituitary & ovarian desensitization (GnRH agonist)

• Poor responder, age > 35 years

Luteinzing hormone

• Predict the ovarian response to gonadotropins.

• Monitor effect of pituitary down-regulation.

• Evaluate whether the dose of gonadotropin is

adequate.

• Avoid OHSS

• Find the optimal time to give hCG

COH monitoring : Why ?


• Trigger ovulation; When?

• 3 follicles of 18 mm (mean of 2 diameters) on Day 9 -10 of stimulation and

• fewer than 15 follicles and

• Endometrial thickness : ≥ 7 mm.

• Drug used to trigger ovulation

• Urinary human chorionic gonadotrophin (uhCG)

• Recombinant hCG (rhCG)

• Recombinant LH (rLH)

• GnRH agonist

Final oocytes maturation / trigger ovulation

Merck & Co., Inc

Success rate

• Success varies with many factors.

• Age of the woman is the most

important factor

• Quality of embryos

• Number of embryos transferred

J Hum Reprod Sci. 2011 Sep-Dec; 4(3): 108–113.

Success rateAge <35 35-37 38-40 41-42 >42

Number of cycles 38662 19599 18410 10167 6224

Percentage of cycles resulting in pregnancies 46.7 37.8 29.7 19.8 8.6

Percentage of cycles resulting in live births 40.7 31.3 22.2 11.8 3.9

Percentage of cancellations 6.3 9.2 12.7 15.8 21.5

Average number of embryos transferred 1.9 2.0 2.4 2.9 2.9

Percentage of live births with twins 29.5 25.0 20.3 13.4 9.0

Percentage of live births with triplets or more 1.1 0.7 0.7 0.7 0.4

Fresh Embryos From Non-Donor Oocytes

2014 SART

art assisted reproductive technology dithawut khrutmuang md

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