art assisted reproductive technology dithawut khrutmuang md
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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
2011 the American Society for Reproductive Medicine
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
2011 the American Society for Reproductive Medicine
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.
2011 the American Society for Reproductive Medicine
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.
2011 the American Society for Reproductive Medicine
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 ?
2011 the American Society for Reproductive Medicine
• 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
Merck & Co., Inc
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