Monitoring ART cycle Aboubakr Elnashar

Monitoring ART cycle
Aboubakr Elnashar
Benha university Hospital, Egypt
Aboubakr Elnashar

CONTENTS
I. METHODS OF MONITORING
II. OBJECTIVES OF MONOTORING
1. Prediction of ovarian response prior to COS
2. Monitor the effect of pituitary down-regulation.
3. Evaluate whether the dose of Gnt is adequate
or not
4. Prevention of OHSS.
5. Find the optimal time to give hCG.
6. Avoid cycle cancellation
III. CONCLUSION 3Aboubakr Elnashar

I. METHODS OF MONITORING
1. US:
 measurements of follicular growth
 endometrial thickness.
2. US and serum E2.
3. Power Doppler imaging
Perifollicular blood flow
4. 3D US.
 TVS is the most practical way {actual response of
ovaries and uterus}
Aboubakr Elnashar

II. OBJECTIVES OF MONOTORING
1. Prediction of ovarian response prior to COS
2. Monitor the effect of pituitary down-regulation.
3. Evaluate whether the dose of Gnt is adequate or
not
6. Prevention of cycle cancellationAboubakr Elnashar

1.Prediction of ovarian response to Gnt
Aim:1. Identify poor responder
2. Identify risk of OHSS
Important:
To choose optimal starting dose of FSH.
Methods: Basal AFC, FSH, AMH
 AFC: superior to basal day 3 FSH. as well as BMI for
predicting the number of oocytes retrieved for lVF.
(Ng et al, 2005)
 ≤6: longer duration
higher dose of Gnt
less oocytes retrieved.
increased risk of cycle cancellation before OR
 ≥16: High responder
Aboubakr Elnashar

2. Monitoring the effect of pituitary down-
regulation.
Before starting follicular stimulation:
confirm down regulation (Criteria of suppression):
Hormonal assay
1. E2 < 50 ng/ml
2. LH < 5.0 IU/ml,
3. P4 < 1 ng/m ng/ml
Aboubakr Elnashar

 TVS:
1. No ovarian cysts
2. Number of small follicles (<8 mm) ≤ 4
3. Endometrial thickness <6 mm predicts down
regulation in 95% of cases
4. Ovarian artery resistance index: 0.9 have the
highest specificity and PPV
If not: stimulation is postponed and the assays
repeated after 2—4 further days of down-regulation.
Aboubakr Elnashar

3. Evaluate whether the dose of GnT is
adequate or not.
1. TVS:
A. 1st US
 D4 Stimulation
In PCO
 D 5 or 6 stimulation
In normal responder
Number: 6-8 each ovary
 With diameter: 11- 12 mmAboubakr Elnashar

B. Follow up
 Daily or Every other day depending on follicle size
 How:
Each follicle is measured in two perpendicular planes.
Then, the average of the four largest diameters is calculated.
 mean of two, three or four diameters, measured in one or two planes.
 Measure the internal diameter of the follicle in two
planes and the average diameter is then calculated.
 Follicles usually grow by 2-3 mm/d.
Aboubakr Elnashar

2. Combining US and E2
In normal responders:
seldom changes the timing of hCG
does not increase PR or the risk of OHSS
(Lass et al, 2003)
E2 D6
300 -600 pg/ml
 D6 E2 < 60 pg/ml: PR 7.8 %
If ok: continue the same dose.
If less than that: increase by one ampoule.
If greater than that: decrease the dose by ½ -1
amp Aboubakr Elnashar

Important in
1. If risk for OHSS.
2. Poor responder
E2 D5 stimulation:
<700 pmol/l: FSH dose is increased by 75-150 u
US on stimulation D9 or 10.
This is a simple way of early discovery that the
starting dose has been sufficient.
3. US monitoring shows adequate follicular growth
but inadequate endometrial growth
{low E production/follicle due to a low endogenous
LH level}: add rec LH
Aboubakr Elnashar

3. Color Doppler
A significant increased oocyte recovery from follicles with a
high peak systolic velocity as measured by pulsed Doppler
and gray-scale ultrasound (Naigund et al, 2007)
Oocytes from poorly vascularized follicles produced
morphologically poor embryos as compared to oocytes from
highly vascularized follicles.
Follicles with normal perifollicular blood flow contained
oocytes free of cytoplasmatic or chromosomal/ spindle
defects. (Van Blerkom et al, 2008)
high-grade follicular vascularity resulted in oocytes/embryos
that had an increased potential for becoming a full-term
pregnancy. (Chui et al, 2009)
Quantitative and qualitative assessment of peri-
follicular flow allow for a more accurate assessment of
follicular competence. Follicles that have >75% of
their surface perfused, or where PSV is >10 cm/s,
appear to contain an oocyte of satisfactory quality.
Aboubakr Elnashar

4. Combination of power Doppler angiography
(PDA) and 3D-US
for predicting and monitoring ovarian response in IVF-ET
(embryo transfer) cycles.
technique really improves the monitoring of the cycle is still
unclear.
technique is complicated and time consuming, making it less
practical for the daily monitoring of ART cycles.
Aboubakr Elnashar

 Predicting of hyper-response
1. Previous history of OHSS
2. The presence of PCOS
3. Younger age
4. Lower BMI
5. High AMH
Aboubakr Elnashar

1. US :
a. PCO pattern of response to GnRH before GnT
b. Number of follicles >20
 Number of small & intermediate size (10-14 mm)
>15
 No risk when immature follicles are < 15.
{Number of the immature follicles is more important
than the number of mature follicles in predicting
OHSS.
c. Doppler:
low intraovarian vascular resistance
Combination of E2 & US: best chance for prediction
Aboubakr Elnashar

2. E2: High or rapid slope
<1000 pg/ml: No OHSS
>3000-4000 pg/ml: HCG should be withheld
<3500 pg/mL: No OHSS (Asch et al 2005)
3500-5999 pg/mL: 1.5%
6000 pg/mL: 38%
Cases with severe OHSS are seen with E2 <1500
pg/ml.
Small fraction of cases will be with excessive E2:
slope of rise of E2 is more accurate (considered if
the value is doubled).
Aboubakr Elnashar

Do not trigger ovulation with the intention of fresh
ET in women who have:
E2>3500 pg/ml or
>20 follicles on US
(NICE, 2013)
Aboubakr Elnashar

Ovulation when?
35-42 h after the onset of LH surge which triggers
resumption of meiosis inside the oocyte
HCG when?
3 or more follicles of size ≥17 mm
Endometrial thickness more than 8 mm
Aboubakr Elnashar

OR when?
When most of the follicles are large enough to
suggest the presence of mature oocytes.
Optimal oocyte recovery and fertilization rates can
be obtained from follicles between 14 and 24 mm in
diameter.
Oocyte recovery rates start to decrease after the
follicles exceed 24 mm in diameter.
No difference in the oocyte quality obtained from
follicles between 18 and 22 mm in diameter: more
convenient and predictable planning of oocyte
collection.
At least 35 h after HCG
Aboubakr Elnashar

US signs of impaired implantation at the time of
hCG administration
1. An endometrial thickness of <7 mm
2. Endometrial volume <2 cm3
3. Endometrial thickness >14 mm
4. Absence of multilayered endometrium
5. Uterine artery PI >3.0
6. Absence of subendometrial or reduction in the
endometrial vascularized area
Aboubakr Elnashar

If Endometrial thickness ≤7
1. Prolong ovulation induction until endometrial
thickness of >7 mm is achieved.
2. If pregnancy is not achieved, in a subsequent
cycle the ovulation induction regimen is changed
to allow for a better endometrial development.
Aboubakr Elnashar

6. Cycle cancellation
Define:
discontinuation of ovarian stimulation prematurely
without oocyte retrival.
Incidence
12% of all IVF cycles are cancelled before egg
collection.
Women's age Cancellation rate
Less than 35 7.7-10%
35-37 11.6-14.7%
38-40 14.6-19.5%
Over 40 19.1-24.6%
Aboubakr Elnashar

The main reasons
1.No or poor egg production (83%)
2.Patient’s personal reasons (10%)
3.Excessive response to ovarian stimulation and
risk of developing OHSS (5%)
4.Medical illness (1%).
(SART 2005 and HFEA 2006 Reports).
AMH:
all cases that was cancelled due to poor response
had AMH < 0.4 ng/ml. (La Marca et al., 2006)
all cases that was cancelled due to high risk of
OHSS had AMH >7 ng/ml.
Aboubakr Elnashar

Indications
1. Follicular growth is delayed:
ovarian stimulation over 10 days:
< 3 follicles > 16 mm & E2 < 600 pg/ml.
2.OHSS is suspected:
each ovary contains > 10 follicles < 16 mm &
E2 > 3500 pg/ml
Ovary size > 80 mm
3. Basal LH is elevated:
LH > 10 IU/l or a premature LH surge occurs
4. Elevated serum P4:
>1.5 ng/ml is detected prior to ovulation induction.
Aboubakr Elnashar

CONCLUSION
Two-dimensional ultrasound scanning of follicular
size is still the method of choice for monitoring IVF
cycles, irrespective of the protocol used for COH.
It is the most practical, and is still reliable enough
for monitoring ovarian stimulation with
gonadotropins.
Combining ultrasound monitoring of follicular size
with E2 is particularly valuable for monitoring poor
responders as well as those at risk for OHSS.
Aboubakr Elnashar

Monitoring ART cycle Aboubakr Elnashar

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