College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
Unnecessary investigations in reproductive medicine
1. 11/2/2021
1
UNNECESSARY INVESTIGATIONS
IN
REPRODUCTIVE MEDICINE
Prof. Aboubakr Elnashar
Benha University, Egypt
ABOUBAKR MOHAMED ELNASHAR
SOURCES
1. ESHRE, 2000, 2017, 2019
2. ACOG, 2019
3. ASRM, 2019
4. Human Fertilisation&Embryology Authority (HFEA), 2019
5. BFS, 2020
6. CFS, 2020
7. American Society for Clinical Pathology2020
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
2
CONTENTS
I. UNNECESSARY INVESTIGATIONS IN
1.INFERTILITY
2.IVF
3.RIF
4.RPL
5.OTHERS
II. CAUSES
III. HOW TO REDUCE UNNESSARY INVESTIGATIONS
ABOUBAKR MOHAMED ELNASHAR
1.INFERTILITY
ABOUBAKR MOHAMED ELNASHAR
2. 11/2/2021
3
ESHRE, 2000
Infertility testing should be classified into 3 groups
depending on correlation with pregnancy rates
I. Tests that have an established association with pregnancy:
1. Conventional semen analysis
2. Tubal patency tests
3. Tests of ovulation
ABOUBAKR ELNASHAR
ABOUBAKR MOHAMED ELNASHAR
II. Tests that are not consistently associated with pregnancy:
Post-coital test
Antisperm antibody tests
Zona-free hamster egg penetration test
III. Tests that have no association with pregnancy:
Premenstrual endometrial biopsy
Varicocele assessment
Chlamydia testing
ABOUBAKR ELNASHAR
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
4
ACOG, ASRM, 2019
Not indicated
1. Post coital testing
2. Thrombophilia testing
No benefit if no history or family history of clotting
3. Immunologic testing
It is expensive & does not predict pregnancy outcome.
4. SDF:
There is insufficient evidence to recommend the routine use
of SDF testing in evaluation and treatment of infertile couple
{level C}
ABOUBAKR MOHAMED ELNASHAR
Not routinely indicated
1. Endometrial biopsy: Except in
suspected T.B. or
endometrial hyperplasia
2. Laparoscopy for unexpl infertility: Unless suspicion of pelvic pathology
3. Prolactin: Except in
abnormal menstrual cycles or
galactorrhea
4. SDF: Indicated in clinical varicocele + borderline /normal semen
5. Karyotype: Indicated in
↑FSH at <40 Y or
abnormal sexual development
ABOUBAKR MOHAMED ELNASHAR
3. 11/2/2021
5
The PCT
suffers from poor reproducibility
predictive value for pregnancy is no better than chance.
Utilizing the PCT:
more tests and treatments
no improvement in cumulative PR.
ABOUBAKR MOHAMED ELNASHAR
Endometrial biopsy for
Histologic dating
does not distinguish fertile from infertile women.
Chronic endometritis
does not predict the likelihood of pregnancy in general nor
is it associated with LBR in ART cycles.
Endometrial biopsy should not be utilized in the routine
evaluation of infertility.
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
6
Prolactin testing as part of the routine infertility evaluation
in women with regular menses.
It has become common practice to obtain prolactin levels in
the routine infertility evaluation.
No reason to expect that a woman would exhibit clinically
significant, elevated prolactin levels in the presence of
normal menstrual cycles and
without galactorrhea.
Serum testing of prolactin levels in a normally menstruating
woman without galactorrhea
provides no benefit
would not impact clinical management.
ABOUBAKR MOHAMED ELNASHAR
Diagnostic laparoscopy if
there is a suspicion of pelvic pathology based on clinical
history,
an abnormal pelvic exam or
abnormalities identified with less invasive testing.
Normal HSG or the presence of a unilaterally patent tube
diagnostic laparoscopy will not change the initial
recommendation for TT.
ABOUBAKR MOHAMED ELNASHAR
4. 11/2/2021
7
Don’t perform advanced sperm function testing, such as
sperm penetration or hemizona assays, in the initial
evaluation of the infertile couple.
extreme variability exists among these tests
very little correlation between results & outcomes.
not to be cost-effective
often lead to more expensive treatments.
ABOUBAKR MOHAMED ELNASHAR
Don’t routinely order thrombophilia testing on patients
undergoing a routine infertility evaluation.
no indication to order these tests
not a part of the infertility workup.
no benefit in absence of
history of bleeding
abnormal clotting
family history.
Testing
costly
: proposed treatments, which would not be indicated in
this routine population.
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
8
Thrombophilia screening.
Not recommended
Before IVF (NICE, 2013)
RPL: only APS (ESHRE, 2017)
RIF (BFS, 2020)
Complicated pregnancy (ACOG, 2015)
ABOUBAKR MOHAMED ELNASHAR
• Why thrombophilia screen shouldn’t b
• Expensive and time-consuming.
• Positive results often cause unjustified concerns and
unjustified medications ending in harming your patient
medically, emotionally, and financially.
• Making a false diagnosis takes you away from true
diagnosis.
ABOUBAKR MOHAMED ELNASHAR
5. 11/2/2021
9
Don’t perform immunological testing as part of the routine
infertility evaluation.
Diagnostic testing of infertility requires evaluation of factors
involving
Ovulation
fallopian tube patency and
spermatogenesis based upon clinical history.
immunological factors
may influence early embryo implantation,
Routine immunological testing
Expensive
does not predict pregnancy outcome.
ABOUBAKR MOHAMED ELNASHAR
2. IVF
1. Before
2. During
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
10
Hysteroscopy
Before the 1st trial of IVF?
(inSIGHT): a multicentre, RCT (Smit et al, 2016, Lancet)
Women with a normal TVS should not be offered
routine hysteroscopy.
ABOUBAKR MOHAMED ELNASHAR
During (cycle monitoring)
The addition of E2 measurements to US monitoring
is probably not recommended.
Conditional ⊕⊕
Based on the evidence, monitoring using E2 &US is not
superior to monitoring by US alone in terms of
Efficacy &
Safety
ABOUBAKR MOHAMED ELNASHAR
6. 11/2/2021
11
The addition of a hormonal panel consisting of a
combination of E2, progesterone& LH measurements
to US monitoring is probably not recommended.
Conditional ⊕
According to one RCT, monitoring using hormonal panel
assessments (E2, LH, P) & US not superior over
monitoring by US alone in terms of
Efficacy
Safety .
ABOUBAKR MOHAMED ELNASHAR
Routine monitoring of endometrial thickness
during COS is probably not recommended.
Conditional ⊕
There are indications that thin endometrium is related to
lower CPR, but:
Thin endometrium is infrequent (2-5%).
Interventions to correct thin EMT have
Little rational basis&
Should be abandoned until contrary evidence arises.
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
12
The guideline group suggests performing a single
measurement of the endometrium assessment on
Day of triggering or
Oocyte pick-up
To counsel patients on potential lower pregnancy
chance.
GPP
A single US assessment is necessary to identify patients with very thin or very thick EMT,& appropriate diagnostic work-up should be done.
ABOUBAKR MOHAMED ELNASHAR
E2 level:
is not recommended to base timing of final oocyte
maturation triggering.
Strong ⊕
No study has been performed assessing the use of E2 as a criterion for
when to trigger final oocyte maturation.
ABOUBAKR MOHAMED ELNASHAR
7. 11/2/2021
13
E2/follicle ratio.
is not recommended to base timing of final oocyte
maturation. Strong ⊕
The association of E2-to-follicle ratio with clinical outcomes
has been studied in observational studies, but
recommendations cannot be derived from these
observational data.
E2-to-follicle ratio will vary depending on
Size of the growing follicular cohort
Distribution of follicles between different size classes
Endocrine situation of the patient
endocrine milieu of the stimulation cycle.
ABOUBAKR MOHAMED ELNASHAR
PGS
Does PGS increase PR in IVF?
Moniek Twisk et al., Hum Reprod; 20013
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
14
Cost-effectiveness analysis of PGS and IVF Vs. expectant
management in patients with unexplained RPL (Murugappan, et al.,
Fertility Sterility, 2015)
LBR and miscarriage
53% and 7%.in IVF/PGS
67% and 24% in expectant.
PGS 100-fold more expensive
IVF/PGS not cost-effective
LBR with IVF/PGS needs to be 91% to be cost effective
compared with expectant.
ABOUBAKR MOHAMED ELNASHAR
3. RIF
Human Fertilisation&Embryology Authority (HFEA), 2019
British fertility society, 2020
Canadian fertility society, 2020
ABOUBAKR MOHAMED ELNASHAR
8. 11/2/2021
15
In 2019: Human Fertilisation&Embryology Authority (HFEA)& 10
other professional& patient bodies
Clear & reliable information about some add-ons
Developed traffic-light rated list of add-ons
Should not be recommended for routine use.
Further research is required
Should only be offered in a research setting.
Patients should not be charged extra to take part in research
ABOUBAKR MOHAMED ELNASHAR
I. ENDOMETRIAL
1. Anatomical:
1. 3 DUS: Green
2. Screening hysteroscopy: Red
3. ERA: Red
2. Immunological
1. uNK cells: Amber
2. pNK cells: Red
3. uCytokines: Red
4. pCytokines: Red
5. Genital micobiome: Red
6. HLA incompatability: Red
3. Thombophilia:
1. APA: Amber
2. Congenital thrombophilia: Red
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
16
II. GAMETE/EMBRYO
1. Sperm:
1. Sperm aneuplody: Amber
2. DNF: Amber
3. Sperm epigenetis: Red
4. CASA: Red
2. Oocyte:
AMH: Amber
3. Genetic testing:
Karyotype: Red
Amber: High order RIF or addional risk factor
ABOUBAKR MOHAMED ELNASHAR
Hysteroscopy
Before IVF in women with RIF (2-4):
(TROPHY): multicentre, RCT
Hysteroscopy before IVF in women with a normal TVS
and a history of unsuccessful IVF does not improve LBR (El-
Toukhy , 2016, Lancet)
ABOUBAKR MOHAMED ELNASHAR
9. 11/2/2021
17
III. OTHER
1. Hydrosalpinx: US: Green
2. Endocrine:
1. TSH: Green
2. Tab: Amber
3. PRL: Red
4. FAI: Red
5. HbA1c: Red
ABOUBAKR MOHAMED ELNASHAR
4. RPL
(ESHRE, 2017)
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
18
Thrombophilias Not recommended
1. Factor V Leiden mutation
2. Prothrombin gene mutation,
3. Protein s deficiency (RCOG, 2011)
4. Hyperhomocysteinemia
In the absence of consistent evidence for an association
between HHcy and RPL
Assessing Hcy levels is not routinely recommended.
Protein C deficiency
Antithrombin III deficiency
ABOUBAKR MOHAMED ELNASHAR
Infections:
Chronic endometritis: Further research is needed before
screening for endometritis can be recommended (ESHRE,
2017)
TORCH test not recommended
Not a cause
Toxoplasmosis, Mycoplasma
L. monocytogenes, C. trachomatis
HSV, CMV
Cultures for bacteria, virus: not recommended
ABOUBAKR MOHAMED ELNASHAR
10. 11/2/2021
19
Immunological: Not recommended
Parental human leukocyte antigen (HLA)
Maternal antipaternal antibodies
ABOUBAKR MOHAMED ELNASHAR
Cytogenetic analysis of products of conception of 3rd and
subsequent consecutive miscarriage(s).
not routinely recommended but
could be performed for explanatory purposes
Parental peripheral blood karyotyping of both partners where
testing of products of conception reports an unbalanced
structural chromosomal abnormality.
not routinely recommended.
could be carried out after individual assessment of risk. S
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
20
5. Others
ASRM, 2019
ABOUBAKR MOHAMED ELNASHAR
Don’t obtain a karyotype as part of the initial evaluation
for amenorrhea.
A karyotype (chromosomal analysis) is not indicated as an
initial test for amenorrhea as it is not a screening test.
However, it is indicated to
further evaluate the etiology of an elevated FSH in a
woman under 40 y
physical findings suggestive of disorders of sexual
development.
ABOUBAKR MOHAMED ELNASHAR
11. 11/2/2021
21
Don’t obtain FSH levels in women in their 40s to identify
the menopausal transition as a cause of irregular or
abnormal menstrual bleeding.
Menstrual bleeding patterns for women after age 40:
less predictable than in the younger years due to the
normal menopausal transition.
Menopause
absence of menstrual periods for one year when no other
cause can be identified
often accompanied by symptoms such as hot flashes and
night sweats
ABOUBAKR MOHAMED ELNASHAR
During this time, blood levels of FSH vary both
from woman to woman and
from day to day in the same woman.
An FSH level does not
predict when the transition to menopause will occur
diagnose that it has begun or
provide reassurance that contraception is no longer
necessary.
Change treatment of irregular or abnormal bleeding
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
22
American Society for Clinical Pathology2020
Don’t order multiple tests in the initial evaluation of a patient
with suspected non-neoplastic thyroid disease.
TSH and if abnormal, follow up with additional evaluation or
TT depending on the findings.
TSH test
can detect subclinical thyroid disease in patients without
symptoms of thyroid dysfunction.
TSH value within the reference interval excludes the
majority of cases of primary overt thyroid disease.
If the TSH is abnormal, confirm the diagnosis with free
thyroxine (T4). ABOUBAKR MOHAMED ELNASHAR
Don’t perform population based screening for 25-OH-Vit D
deficiency.
Vit D deficiency is common in many populations, particularly
in patients at higher latitudes, during winter months and in
those with limited sun exposure.
Over the counter Vit D supplements and increased summer
sun exposure are sufficient for most otherwise healthy
patients.
Laboratory testing is appropriate in higher risk patients when
results will be used to institute more aggressive therapy
(e.g., osteoporosis, chronic kidney disease, malabsorption,
some infections, obese individuals).
ABOUBAKR MOHAMED ELNASHAR
12. 11/2/2021
23
Don’t perform low risk HPV testing.
National guidelines provide for HPV testing in patients with
certain abnormal Pap smears and in other select clinical
indications. The presence of high risk HPV leads to more
frequent examination or more aggressive investigation (e.g.,
colposcopy and biopsy).
There is no medical indication for low risk HPV testing (HPV
types that cause genital warts or very minor cell changes on
the cervix) because the infection is not associated with
disease progression and there is no treatment or therapy
change indicated when low risk HPV is identified.
ABOUBAKR MOHAMED ELNASHAR
Don’t use bleeding time test to guide patient care.
The bleeding time test is an older assay that has been
replaced by alternative coagulation tests. The relationship
between the bleeding time test and the risk of a patient’s
actually bleeding has not been established. Further, the test
leaves a scar on the forearm.
There are other reliable tests of coagulation available to
evaluate the risks of bleeding in appropriate patient
populations.
ABOUBAKR MOHAMED ELNASHAR
11/2/2021
24
Don’t order ESR to look for inflammation in patients with
undiagnosed conditions. Order a C-reactive protein (CRP)
to detect acute phase inflammation.
CRP is a more sensitive and specific reflection of the acute
phase of inflammation than is the ESR. In the first 24 hours
of a disease process, the CRP will be elevated, while the
ESR may be normal.
If the source of inflammation is removed, the CRP will return
to normal within a day or so, while the ESR will remain
elevated for several days until excess fibrinogen is removed
from the serum.
ABOUBAKR MOHAMED ELNASHAR
CAUSES
1. Patient Pressure
2. Fee incentive.
3. Business development
4. Lack of Knowledge
5. Defensive Medicine, More is Safer
ABOUBAKR MOHAMED ELNASHAR
13. 11/2/2021
25
HOW TO REDUCE UNNESSARY INVESTIGATIONS
1.Diagnostic Algorithms
2.Evidence Based investigations
3.Cost effectiveness
4.System Approach
5.Respected professionals should reach out to the
media and propagate good, ethical evidence based
practice
6.Critical analysis and not believing all claims and not
publicsing bad research
ABOUBAKR MOHAMED ELNASHAR