Recurrent pregnancy loss Presentation by Dr.Laxmi Shrikhande

Dr. LaxmiShrikhande
MD;FICOG;FICMU
Director-Shrikhande Fertility Clinic, Nagpur
President Menopause Society, Nagpur
National Corresponding Editor-The Journal of Obstetrics & Gynecology of India
Senior Vice President FOGSI 2012
Vice Chairperson Indian College OB /GY
Governing Council member ICOG 2012-2017
Governing Council Member ISAR 2014-2019
Governing Council Member IAGE for 3 terms
Patron-Vidarbha Chapter ISOPARB
Chairperson-HIV/AIDS Committee, FOGSI (2007-09)
Received Best Committee Award of FOGSI
Received Bharat excellence Award for women’s health
President Nagpur OB/GY Society 2005-06
Associate member of RCOG
Member of European Society of Human Reproduction
Visited 96 FOGSI Societies as invited faculty
Delivered 3 orations
Publications-Thirteen National & seven International
Presented Papers in FIGO, AICOG, SAFOG, AICC-RCOG conferences
Conducted adolescent health programme for more than 15,000 adolescent girls

Recurrent Pregnancy loss
DR LAXMI SHRIKHANDE
NAGPUR

Introduction
Emotionally traumatic, similar to stillbirth or neonatal death
Primary / secondary / Tertiary
Primary RPL- refers to multiple losses in a woman with no previous viable infants,
secondary RPL refers to multiple losses in a woman who has already had a pregnancy beyond 20
gestational weeks
Tertiary RPL refers to multiple pregnancy losses between normal pregnancies
◦Better prognosis with secondary and Tertiary
Terminology for pregnancy loss prior to viability : a consensus statement from the ESHRE early pregnancy special interest group.
Hum Reprod 2015;30(3):495-498
Nomenclature for pregnancy outcomes : time for a change. Obstet Gynecol 2011 ; 118(6): 1402-1408

RPL – basic facts
1% of women have recurrent miscarriages
A majority of women do not have an identifiable cause
At least 70% of women have a successful pregnancy
outcome in the subsequent pregnancy
ACOG Practice Bulletin No.24, 2001
RCOG GreenTop Guideline No.17, 2003

Recurrent Miscarriage
Recurrent Miscarriage Definitions
◦ 3 or more consecutive pregnancy losses (UK)1
◦ 2 or more consecutive pregnancy losses (USA)2
◦ Miscarriage as loss of fetus weighing ≤ 500g, which would
normally be at 20-22 complete weeks of gestation (WHO)3
1. Royal College of Obstetricians and Gynaecologists 2011. The Investigation and Treatment of Couples with
Recurrent First-trimester and Second-trimester Miscarriage, [Guideline no. 17]. London, UK.
2. 2. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril 2008; 90(5 Suppl): S60.
3. 3. Pokale YS. Int. Res. J. Medical Sci. 2015;3(9):13-19

Etiology
Established causes of recurrent miscarriage include
 immunological (20-50%),
endocrine (17-20%),
anatomical (12-16%),
genetic (5%), and
infection (0.5-1.5%).

Evaluation
It includes taking
history,
physical examination and
appropriate investigations which differ with the trimester though there is an
overlap.1
1) Evaluation and management of recurrent early pregnancy loss.
Stephenson M, Kutteh W.Clin Obstet Gynecol. 2007 Mar;50(1):132-45.

History
Gestational age of the loss. Chromosomal & endocrine earlier than anatomic or immunological causes
Irregular menstrual cycles or galactorrhoea suggestive of possible Endocrine dysfunction/ Hyperprolactinemia
Consanguinity/ family h/o congenital abnormalities/early losses - Genetic
Uterine instrumentation- possible intrauterine adhesions
Exposure to exogenous agents like bisphenol A and concurrent noxious agents is difficult to recall, document and
to measure the toxin dose.
Radiation and Chemotherapeutic agents, chemicals.
Alcohol and caffeine intake are toxic to the embryo in a dose-dependent manner.
Cigarette smoking,
H/o thrombosis - APLA
PCOS
Information from previous laboratory, pathology, and imaging studies

Examination
General-Signs of endocrinopathy (hirsutism, galactorrhea, thyroid)
Systemic
Gynec
TVS

Investigations recommended for recurrent miscarriages
Investigation Recommendation If required
Genetic - Karyotype Parental and fetal
Anatomical Two-dimensional/
three-dimensional
ultrasonography and
sonohysterography
Hysteroscopy, laparoscopy, or
magnetic resonance imaging
Thrombophilia Acquired APS Inherited
Infection Chlamydia, Endometrial
biopsy and culture
Immunological Antinuclear antibody
Endocrine Thyroid -TSH, Antibodies Prolactin,HbA1C
Male factor Sperm DNA fragmentation
index

Male factor-
Some studies suggest that DNA fragmentation is increased with RPL,
especially in the in vitro fertilization setting.
The ASRM guidelines state that routine sperm DNA fragmentation
indexing is not indicated because of the weak evidence, but
 the ESHRE guidelines state that this can be done to provide an
explanation for RPL.

Recurrent Miscarriage-Maternal causes
Recommended Investigations to Search for Causes (UK)1
1. Royal College of Obstetricians and Gynaecologists 2011. The Investigation and Treatment of Couples with
Recurrent First-trimester and Second-trimester Miscarriage, [Guideline no. 17]. London, UK.
Antiphospholipid antibodies Karyotyping
Anatomical factors Thrombophilias

Antiphospholipid Antibody Syndrome
and
RPL

Usually an over diagnosed syndrome
Not meeting clinical and the strict laboratory criteria
Not repeating the laboratory test at 6 weeks
Non standardized ELISA for ACL antibodies
Inter laboratory variations for phospholipid dependent coagulation
tests used for screening for lupus anticoagulant
Pitfalls in diagnosis of PAPS

Which anomaly ?
General Infertile Recurrent
Miscarriage
Hypoplastic 0 0.7 0
Unicornuate 0.03 0.4 0.4
Didelphys 0.03 0.2 0.1
Bicornuate 0.3 0.8 1
Septate 2 3.5 5
Arcuate 4.9 1.9 12.2
T shaped 0 0 0.6
Saravelos H et al, Hum Rep Update 2008

Diagnosis of uterine anomalies
Hysteroscopy with laparoscopy is the gold standard
Sonosalpingography and 3D ultrasound have more than
90% accuracy
Hysteroscopy is the only one which allows a “see-and-
treat” approach

DIAGNOSIS OF Cervical Insufficiency
History of painless repeated mid trimester spontaneous
miscarriage or premature delivery
Manual estimations
Ability to introduce a number 8 Hegar dilator through the
internal os when patient is not pregnant.
Hysterosalpingogram demonstrating cervical funneling.
Clinical evidence of extensive obstetric or surgical trauma to
cervix.

Immunotherapy
Paternal cell immunisation, third-party donor leucocytes,
trophoblast membranes and intravenous immunoglobulin in women
with previous unexplained recurrent miscarriage does not improve
the live birth rate.
Porter TF et al. Cochrane Database Syst Rev 2006:
◦ Provides no significant beneficial effect over placebo in preventing
further miscarriage
Harrison RF. Eur J Obstet Gynecol Reprod Biol 1992;47:175–9.
Quenby S, Farquharson RGFertil Steril 1994;62:708–10.

Inherited thrombophilias
Insufficient evidence to evaluate effect of heparin in pregnancy to
prevent miscarriage in women with recurrent first-trimester
miscarriage associated with inherited thrombophilia
Heparin therapy during pregnancy may improve live birth rate of
women with second-trimester miscarriage associated with inherited
thrombophilias
Harrison RF. Eur J Obstet Gynecol Reprod Biol 1992;47:175–9.
Quenby S, Farquharson RGFertil Steril 1994;62:708–10.

Endocrinal factors
Luteal phase defects
Thyroid replacement therapy
Optimizing HBA1c levels
Correct hyperprolactinaemia
Polycystic ovaries ? metformin

 No definite recommendations for routinely
obtaining abortus karyotype (ACOG 2001)
 Karyotype analysis of abortus tissue for couples with a subsequent
second or third pregnancy loss (Hogge, et al 2003)
 If abortus is aneuploid, maternal cause is excluded (ACOG, 2001)
 If POC karyotype not possible, do parental karyotype

Unexplained RPL
50% of RPL remain unexplained
Prognosis is still good
◦>50 % live birth even without intervention

Conclusion
RPL is an important reproductive health issue. Various etiologies have identified
over the years and successful therapeutic strategies implemented.
A full workup can be initiated following two consecutive losses to identify
treatable causes that include uterine abnormalities, APS, endocrine diseases,
and balanced translocations.
Lifestyle modifications should also be implemented to improve reproductive
prognosis. However, almost half of the cases remain unexplained, for which
various treatments are continuously being developed.
Regardless of the cause, a thorough follow up with an important psychological
support can help most couples achieve a successful live birth

Dr. Laxmi Shrikhande
Shrikhande Hospital & research Centre
Ph-96234 59766 / shrikhandedrlaxmi@gmail.com

Recurrent pregnancy loss Presentation by Dr.Laxmi Shrikhande

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Recurrent pregnancy loss Presentation by Dr.Laxmi Shrikhande