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A little bit pregnant Biochemical Pregnancy/ Lost Pregnancy/ pregnancy today and not tomorrow… Chemical pregnancies are the most frustrating and heartbreaking situation for couples longing for a baby. They fail to understand how a pregnancy diagnosis today can turn into no pregnancy tomorrow therefore it looks like a mystery hunt. It is the most difficult situation to handle with a complete loss of control.
BIOCHEMICAL PREGNANCIES – “THE UNSOLVED MYSTERY”

Biochemical pregnancy meaning – what is the cause? Why did this happen to me?????
What to do next?
DID I DO SOMETHING WRONG???
Implications of these pregnancies on subsequent pregnancies?
IS MY UTERUS DEFECTIVE???
WILL I NEVER HAVE A BABY???

What is biochemical pregnancy?

In a biochemical pregnancy, hCG levels decline and pregnancies are diagnosed only by chemical means i.e., urine or more precisely a blood pregnancy test but not further visualized on ultrasound scans.

They are to be differentiated from ectopic pregnancy. Therefore, a follow-up is very important.

Biochemical pregnancy symptoms

What are Signs and Symptoms of Biochemical Pregnancy?

  • You will have late menstrual periods than usual
  • Heavier than normal menstrual period
  • More menstrual cramping
  • You don’t see any signs of early pregnancy in spite of positive pregnancy test

How frequently are they seen?

In a natural spontaneous conception, 1/3rd of all the pregnancies implanted go unnoticed as the woman doesn’t even realize that she was pregnant, unless she is trying for conception & is regularly testing.

But more realized after IVF which has come into common practice because occurrence of pregnancy is always confirmed by a blood workup test.

What is the mechanism of biochemical pregnancy?

Soon after fertilization or ET, the embryo begins to secrete B hCG. Trophoblastic reaction and embryo invasion continues resulting in continuous rise in hCG levels. Pts test is positive in the early stages. Further growth stops thus preventing any further evidence of pregnancy on USG.

The truth is biochemical pregnancy is a conception but actually a very early miscarriage.
Genetically abnormal embryo (weak or poor quality) -developmental arrest and degeneration.

biochemical pregnancy

Diagnosis of biochemical pregnancy:

As pregnancy is not visualized, most biochemical pregnancies go unrecognized
Low peak serum beta hCG levels are < 100 IU.
If after an initial good beta hCG levels, the levels decline/ rapid fall in levels.
In spite of the beta hCG test being positive, pregnancy fails to progress to the point of USG confirmation.
In IVF, pregnancy cannot be visualized after 5 to 5.5 wks or 3 to 3.5 wks after EMBRYO TRANSFER.

What could be the probable causes of biochemical pregnancy losses?

  • Could be maternal, that is, in the female partner or paternal/male partner or maybe both or maybe both are normal but there is some problem of embryo development the risk factors include maternal age extremes of BMI, smoking, and stress.
  • Other causes could be immunological factors, presence of all immunity, autoimmunity, endocrine factors like diabetes or presence of he has hyperprolactinemia, LPD, thyroid diseases.
  • There may be some uterine factors like congenital abnormality(shape) or hydrosalpinx. Sometimes we only find a poor endometrial lining(<9mm).
  • There could be some problem with endometrial receptivity. Cause could be some infection which may be there in the uterus. It could be related to antiphospholipid antibody syndrome.
  • Apart from all these causes, not to be forgotten may be “sub-optimal” lab culture conditions which are often overlooked. Conditions inside the lab namely some pollutants of air pollution or VOC are to be checked.

Chromosomal abnormalities:

Almost 50% of early pregnancy losses take place due to chromosomal abnormalities, mostly aneuploidy. Preimplantation Genetic Testing (PGT) can be offered to rule out chromosomal aneuploidies in embryos before transfer.

AGE is a very important prognostic indicator.

WOMEN’S AGE- aneuploidy rate 25%-, 35yrs, 50%-
Higher rates of biochemical pregnancy losses in advanced maternal age due to higher incidence abnormal aneuploid eggs, diminished ovarian reserve Increasing rate of embryo- endometrial asynchrony.

Can male partner also be responsible for a biochemical pregnancy?

Sperm DNA damage indicated an association of significantly increased risk of pregnancy loss after IVF Treatment/ICSI Treatment.

UTERINE FACTORS

Congenital uterine abnormalities –septum or unicornuate.
•Presence of a myoma or a polyp in the cavity.
•Adenomyotic uterus or presence of endometriosis.
•Hydrosalpinx.

THIN ENDOMETRIUM

•Previous endometrial traumas
•Prolonged use of OCP
•Impaired uterine blood flow

INFECTIONS /CHRONIC ENDOMETRITIS

•Diagnosis-histological confirmation after hysteroscopic visualization
•Bacterial cultures
•Immunohistochemistry

PRESENCE OF PLASMA CELL

Molecular diagnosis is more promising like RT PCR –diagnose bacterial DNA 75% sensitivity and 100%
Specificity.

IMMUNOLOGICAL CAUSES

Maternal immune system is a very important determinant in selecting or rejecting the embryo.

PRESENCE OF AUTOIMMUNE ANTIBODIES

Antiphospholipid antibodies, Antithyroid antibodies (Peroxidase & Thyroglobulin), Anticardiolipin Antibodies, Anti B2 glycoproteins, Lupus Anticoagulants

Treatments in present pregnancy

No specific treatment. Chemical pregnancy is short lived, so no time for treatment. Follow up with beta hCG levels test the declining levels to undetectable values in order to differentiate from ectopic pregnancy. May be a non-viable or persistent (PUL), MTX may be required. Prognosis of future pregnancy not affected.

If a biochemical pregnancy has occurred, feedback from the lab regarding the quality of eggs, sperms & embryo should be obtained to identify any problem in order to rectify it.

pregnancy treatment

LIFESTYLE MODIFICATIONS

•Exercise
•Diet
•Nutraceuticals
•Quit Smoking, Tobacco
•Alcohol
•Correction of metabolic & endocrinal causes.

THERAPEUTIC INTERVENTIONS

Various strategies during IVF-ET are adopted
•Change the protocol
•Take her for blastocyst transfer instead of day 3 transfer
•We can free all and do a segmental IVF
•PRP instillations

TREATMENT OPTIONS FOR RECURRENT BIOCHEMICAL PREGNANCIES

Anatomical – SALPINGECTOMY, fibroid/ polyp removal treatment for endometrial growth
Thrombophilia – LMWH, LDA
Genetics – ERA, PGT-A, KARYOTYPING
Immunological – IVIG, G-CSF
Infection – ANTIBIOTICS PRP instillation, G-CSF
Embryo – PFT-A
Male Factor – Stop Smoking, IMSI
IVF Protocol – Optimize Protocol
Personalized Medicine

SIGNIFICANCE OF BIOCHEMICAL PREGNANCY

How do they affect future pregnancies??
Not necessary once a biochemical will have difficulty in conceiving
Any pregnancy that has occurred indicates that “THERE IS A BIG HOPE” for the future.

How soon can a woman get pregnant again after biochemical pregnancy loss?

A woman can attempt pregnancy almost immediately after an early pregnancy loss.

CONCLUSIONS

  • Physicians as well as patients are under great pressure to know the cause of BCP & treatment for future pregnancy attempts.
  • Although it sounds like a false pregnancy, as if the patient was not pregnant at all.
  • Not only meticulous workup but also communication with the Best IVF Center is very important to find out the cause of mishap in this pregnancy and treatment for the next pregnancy.
  • Biochemical pregnancy is definitely not a success, but it surely is a GOOD OMEN, as they are positive predictors of future pregnancies as women who had chemical pregnancy in first IVF are more likely to have a successful outcome in future conceptions.

Dr Shefali Jain

Dr. Shefali Jain is Gynecologist, Obstetrician & Infertility Specialist in Indore with more than 27 years of experience in the field of ART with highest success rate. She has received many awards for her exceptional work in the field of infertility. She has been an invited speaker to many national and international conferences.