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what is the definition of recurrent PG loss (RPL)
3+ spontaneous miscarriages prior to 20 wks gestation
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what is the incidence of RPL
1% of PG women have had at least 2 prior spontaneous abortions
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What is the liklihood of a live birth after 3+ spontaneous abortions
- 70% w. dx of RPL
- 55% if previous live birth has occured
- statistics apply only in young women
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What are the common causes of RPL (7)
- III AGEE
- idiopathic loss
- infectous causes
- immuniologic causes
- anatomic causes
- genetic factors
- environmental factors
- endocrine factors
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What is the liklihood of a parental chromosomal problem in RPL
- 3-8%
- MC balanced translocation
- others- sex chromo mosaicism, chromo inversions, ring chromo
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What is the contribution of fetal chromo abnormalities to RPL
70% of spontaneous miscarrages are associated w. fetal chromo abnormality
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what is the MC fetal chromo abnormality in 1st trimester miscarrages
- MC (50% as a group) in order trisomy 16, 22, 21, 15, 14, 18
- Single MC abnormality is turners 45X (25%)
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what specific environmental factors have been linked to RPL
- tetrachloroethylene (drycleaning)
- ROH
- tobacco abuse
- no longer assoc w. RPL: caffeine, anesthetic gases
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what endocrinopathies are associated w. RPL
- uncontrolled DM
- thyroid dz
- PCOS
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Explain the concept of luteal phase defect (LPD)
- inadequate secretin on progesterone from corpus leutum during secretory phase retards the dev of the endmetrial lining
- the underdev lining is then unable to support a PG and spontaneous abortion results
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How is luteal phase defect (LPD) DX
- endometrial BX near upcoming menses (day 26-27 in a 28 day cycle)- pt notifies Dr. post BX the 1st day of menses (menses = day 28 of cycle)
- or BX during urine LH surge (day 9-10 POST LH surge)
- histologically exam- if there is a lag of 2+ days then LPD may be present
- DX based on two samples from two different cycles
- alternate quick less invasive DX- measure serial mid-luteal progesterone levels- any level less than 10ng/ml may indicate a luteal insuffiency
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How do we TX LPD
- due to poor folliculogenesis any RX that improves follicular development can help
- clomphene citrate
- gonadotropin
- progesterone in luteal phase PO, vaginal or IM (check mid-luteal levels)
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How is RPL related to anatomy
- Type V anomalies (septate)
- congenital mullerian anomalies related to DES exposure
- Asherman syndrome
- Other intrauterine filling defects (submucous myoma)
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Utererine anatomical abnormalities
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What anatomical abnormalities are not related to RPL
- anomalities involving incomplete mullerian fusin resulting in
- type II unicornuate
- Type III didelphys
- type IV bicornate
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How can anatomical defects be detected
- Gold standard HSG
- US
- saline infusion sonography
- MRI to diff between uterine septum or bicornate
- hysteroscopy- more invasive
- laproscopic and hysteroscopy
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What is the appropriate course of action to distinguish between a uterine septum and a bicornate uterus
- If suspected MRI should be performed prior to surgical correction
- if MRI inconclusive -->laproscopic + operative hysteroscopy
- A pt should NEVER be scheduled for hysteroscopic septum removal based on HSG findings due to risk of uterus perforation
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Describe the surgical procedure for correction of a septate uterus
- Procedure of choice: hysteroscopic resection w. 1.5% glycine soln as distention medium
- use continous flow pump during surgery to keep track of fluid balance
- scissors can be used to cut septum in middle, which will usually retract thus no tissue is removed
- alternative approach: use cautery to remove the septum from the bases--may risk scarring of the underlying myometrium
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What is the post op. management of septate removal
- small septum: no post op hormone tx
- otherwise post op estrogen (conjugated estrogen 1.25mg/day x 30 days followed by 10 days overlap w. medroxyprogesterone at the end of the regimen
- post op untrauterine foley placement is rarely indicated
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Why do we have to be very cautious when glycine is used as distention fluid in operative hysteroscopy
- during operative hysteroscopy glycine may gain access to uterine vasculature when vessels are opened during procedure (submucosal resection of myoma)
- because distention medium is under pressure glycine readily passes into vasculature which may lead to hyponatremia, hypo-osmolality and HYPERvolemia --> pul. edema, water intoxication and cerebral edema
- to minimize risks maintain low intrauterine pressure and monitor fluid deficit (total fluid = fluid in + fluid out) by continous flow pump
- any deficit greater than 500 ml = monitor fluids post op
- TX glycine overload- diuresis w. furosemide and monitring of vital signs and electrolytes
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What microorganisms have been implicated in RPL
- Suspected orgs
- Ureaplasma urealyticum
- listeria monocytogenes
- Toxoplasma gondii
- viruses: rubella, herpes, measles, CMV, coxsackie
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Do antibx play a role n TX of RPL
- no routine antibiotics
- if ureaplasma urealyticum grow tx both partners w. doxycycline 100 mg PO x 14days
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What immunologic etiologies have been linked to RPL
- proven: antiphospholipid antibodies
- implicated: anticardiolipin ab, lupus anticoagulant, antithyroid, ANA, phosphadityl serine
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do thrombophilias affect risk for RPL
antiphospholipid antimbodies: only truely established link, more likely to have a thrombolytic event.
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What lab blood tests can be used to r/o thrombophilic etiologies for RPL
- consult a hemotlogist
- order first: aPTT, anticardiolpin ab, ANA, lupus anticoagulant,
- if neg then oreder; antithrombin III, protein C and S, activated protein C resistence ration, fibrinogen, prothrombin G mutation, thrombin time, factor V leiden mutation, homocysteine level, CBC
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TX thrombolic problems associated w. RPL
- ASA 81 mg and prophylactic doses of heparin (5,000 units BID SQ)
- give this TX during entire PG-managed by MFM
- if IVF is to be used- stop ASA and heparin prior to oocyte retrieval
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what should be recommended if pts w. RPL cannot naturally acheive PG
- superovulation agents + IVF or IUI
- use of donor eggs or sperm
- adoption
- serrogate gestational carrier
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If suspect RPL what test should be ordered
- parental and fetal karyotypes
- cervical cultures for mycoplasma and ureaplasma
- HSG or saline sonogram
- TSH, prolactin
- Mid-luteal progesterone levels
- endometrial BX
- autoimmune eval: antiphospholipid ant, ANA, aPTT
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