Transcript individualised ivf treatment - Gynescope Specialist Hospital

INDIVIDUALIZED IVF TREATMENT
BY
DR. JUDE E. OKOHUE
MBBS, FWACS, FMCOG, DMAS, FICS, Cert (USS)
GYNESCOPE SPECIALIST HOSPITAL
PORT HARCOURT.
+2348037275377
WWW.GYNESCOPESH.COM
INTRODUCTION
•Louise Brown 1978
•IVF technology has grown in leaps and bounds
•Success rates have improved drastically
•5 million babies delivered worldwide as at 2012
(ESHRE)
Success:
Innovations in ART laboratory
Optimized by applying an individualized patient
directed approach especially in the mgt of
women undergoing COH

Differences in body physiology and response
to IVF medications

Prior to the first IVF cycle, it is sometimes
difficult predicting the method(s) that suits
the needs of any particular patient
RELEVANT DETAILS FOLLOWING A PRIOR IVF CYCLE
1.
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Type of protocol used
Type/Number of Amps of stimulation drug
Number of days on controlled ovarian
stimulation
Number of oocytes retrieved
Type of treatment (IVF/ICSI)
Number of eggs fertilized
Number of ET/Day of ET
Luteal phase support
Outcome
STRATEGIES FOR INDIVIDUALIZING IVF TREATMENT
Individualizing IVF treatment should
commence the moment the patient presents
to the ART practitioner
 History:
 Helps build patients’ confidence
 General and specific questions
 History of abortion and previous surgeries
 Azoospermic men/ STI
 Children outside wedlock



Every practitioner develops his/her own skills
Patients depend on the dexterity of the
practitioner in obtaining relevant information
Individualized physical examination
 Same principle
 Should not be considered as routine
 Investigations
 Retinue of investigations
 Individualized to meet patients’ needs

CONTROLLED OVARIAN STIMULATION
The most important component of
individualized IVF treatment
 Era of ovarian stimulation with
gonadotropins commenced in the early 80’s
Key components for choosing the appropriate
regimen for COH
 Selection of the appropriate COH protocol
and gonadotropin dosage
 Close monitoring of follicular growth and
serum estradiol levels

•Adjustment
of gonadotropin dosage to avoid
hyper response and therefore OHSS
•Individualized
Central
timing of hCG injection
Question: Will the woman have a good or
poor response to gonadotropin stimulation?
Predictive Factors of Ovarian Response
•Patient characteristics: Age, Parity,
Reproductive history, BMI, Previous response to
ART treatment
•Endocrine markers of ovarian response: Day 2
or 3 FSH, AMH, Estradiol, Inhibin B
•Ultrasonic markers: AFC, Ovarian volume,
Ovarian blood flow
•Dynamic evaluation of ovarian reserve:
Clomiphene citrate challenge test, GnRH
agonist stimulation test, Exogenous FSH ovarian
test. (Limited predictive value – Maheshwani et
al, 2009)
AMH and AFC are the most accurate
predictors of ovarian response to COH (Broer
S. C. et al, 2011)
 AMH:
 Consistent serum levels throughout the
menstrual cycle
 Minimal cycle to cycle variability (Fanchin,
2005)
 <0.99ng/ml = 100% sensitivity and 73%
specificity in predicting poor response
(Jayaprakason k. et al, 2010)

TREATMENT REGIMEN BASED ON PERCEIVED
RESPONSE
1.
Normal Responders
Favourable Prognostic factors
 Age <35years
 Normal BMI
 Adequate ovarian reserve (day 2/3 FSH
<10miu/ml, Estradiol <75pg/ml)
 AFC between 6 and 10
 Short duration of infertility
 Previous live birth
 Previous successful IVF
PROTOCOL:
GNRH
AGONIST SHORT OR
PROTOCOLS
GNRH ANTAGONIST PROTOCOLS
2. High responders: Greatest risk is OHSS
Factors That Increase The Risk of OHSS:
 Young age
 PCO on USS (+ BCH evidence)
 Previous OHSS
 High dose of gonadotropins
 Estradiol levels >3000pg/ml
 Rapidly rising Estradiol levels
LONG
PROTOCOLS (AIM FOR 5 – 15 FOLLICLES)
GnRH antagonist protocol in combination with
GnRH agonist ovulatory trigger. 1,500iu hCG
after GnRH agonist trigger reduces OHSS
(Humaidan P. et al, 2013)
 OCP GnRH dual suppression protocol
 Start with a small dose/few amps of
gonadotropins
 Stimulation drugs with very low LH in PCOS pt
 Long GnRH agonist protocol (longer down
regulation)
 Coasting, reduce hCG dose, freezing, cancel Rx

3. POOR RESPONDERS
No universally acceptable definition
 Prevalence: 10 – 25% (CDC, 2011)
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Determinant Factors
Age > 40years
High FSH >10iu/l
AMH <1.1ng/ml
Previous cancelled cycles
Prolonged duration of COH
Increased daily and total gonadotropins (>44)
<3 to <5 oocytes retrieved
ESHRE consensus working group 2011,
defined poor responders as having at least 2
of the following 3 features
1. Advanced maternal age > 40years or any
other risk factor for diminished ovarian
reserve
2. Previous history of poor ovarian response
(<3 oocytes retrieved with conventional IVF)
3. Abnormal ovarian reserve test (AFC <5 or
AMH < 1.1ng/ml)

PROTOCOLS
GnRH antagonist protocol
 Co-flare and micro-flare protocols
 Japanese Minimal Stimulation Protocol (Mini
IVF)
 Clomid on day 3
 Low dose hMG days 8,10 and 12
 GnRH agonist trigger
 Cryopreservation of embryos
 ET with natural cycle

Agonist/Antagonist conversion protocol
 Can start with OCP
 GnRH agonist after at least 10 days
 Half dose (0.125mg) of GnRH antagonist
when menses starts
 Gonadotropin stimulation after a few days
 Continue antagonist and stimulation drugs
until hCG trigger.
 DHEA

TIMING AND DOSE OF HCG
Should be individualized based on the
following:
 Leading follicle diameter
 Estradiol level
 Prior cycle response and embryo quality
 Type of COH protocol

Normal responders: >2 follicles reach 17mm or
larger/estradiol level >400pg/ml for 5 days
 Previous mostly immature oocytes: Allow leading
follicles to reach 19 – 20mm
 Clomiphene citrate or Letrozole COH protocols:
aim for 19 – 20mm
 Previous poor oocytes or embryo quality
especially with a high proportion of polyspermic
fertilization: Suspect postmaturity and give hCG
at smaller lead follicle diameter
 Plateau or doubling estradiol on consecutive
days with leading follicle >16mm: Give hCG

LUTEAL PHASE SUPPORT

Stimulated IVF cycles are associated with
LPD

No agreement regarding the optimal
supplementation scheme (Faterini et al,
2006)

Lack of RCT on the issues of LPS and the
causes of LPD
STRATEGIES
Progesterone
 Estradiol
 Ascorbic acid
 Aspirin
 Prednisolone
 hCG
 Naxolone

SUMMARY
Individualized IVF treatment optimizes success
rate
 While history, physical examination and
investigations have roles to play in
individualizing IVF treatment, the mainstay is
individualized controlled ovarian stimulation
 AFC and AMH are the most important
predictors of ovarian response

Normal responders can use the long or short
GnRH agonist or GnRH antagonist protocols
 High responders benefit from GnRH antagonist
protocol with GnRH agonist ovulation trigger as
this reduces OHSS
 While there is no universally acceptable
definition of poor responders, the Japanese
mini IVF shows promising results and should be
further investigated
