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Pregnancy despite Implanon®

A thirty-eight-year-old woman came to see her GP as she had fainted twice in the last week. The second occasion was the day of the consultation and her work had suggested she see a doctor. She had only fainted once before in her life, when she had influenza, and she could find no obvious reason for this. As she had felt pre-syncopal very early in her two pregnancies she wanted pregnancy ruled out; she had been amenorrhoeic for eighteen months. She had no other symptoms pertaining to pregnancy. The patient told her GP on questioning that in the past, she had fallen pregnant normally and fairly quickly after several months each time. She was P2, G2, had two children aged five and eight years and did not want more.

The faints were preceded by clear pre-syncopal symptoms and the second time she avoided complete loss of consciousness by sitting with her head between her legs for several minutes. There had been no injuries associated with either episode, no recent illness and no history of recent head trauma. This lady had had Implanon® inserted almost three years previously and already had an appointment with her gynaecologist to have it replaced in two months’ time. She was on no medications and had no medical problems. She looked well but tired, and was of normal weight. Her examination and vital signs were normal.

The GP tested the urine for infection and the urinalysis was negative. The urine test, however, was weakly positive, signifying a pregnancy. The woman was shocked. The test was followed up by a quantitative (as opposed to qualitative) serum BhCG at the time and she was given another pathology form for another quantitative BhCG to be measured in three to five days’ time.  The initial test showed a serum BhCG level of 105U/L, consistent with a four to five weeks’ gestation. The repeat test done four days later showed no detectable BhCG. The patient was informed that she was no longer pregnant.

BhCG is a hormone produced by the placenta and the levels approximately double every two to three days in a normal pregnancy until about twelve weeks, when they plateau off.1   Serum BhCG levels rapidly return to zero, with a half-life of two to three days if the hormone is no longer produced.1 The serum BhCG levels becomes positive one week approximately after conception (i.e. a week before the missed period) at a level of 25U/L.1 The fact that the urine test was positive independently suggests the patient was at least four weeks’ pregnant at presentation, as this is the lower gestational limit of most commercial urinary pregnancy test kits.

The issue of an ectopic was not seriously considered in this patient at the initial presentation due to the extremely low level of pregnancy hormone, the lack of any abdominal pain and then because the pregnancy hormone later became undetectable. However, if the pregnancy were ongoing, the possibility of an ectopic would have needed to be considered, as this is more likely than in natural conceptions with no contraception.2

The product information about Implanon® (etonogestrel implant, 68mg) states clearly that the device should be replaced every three years and in this patient was due to have the device replaced shortly.

Despite this, the Implanon® in this case is still very likely to have affected the implantation of the embryo, given the fact the patient had been amenorrhoeic (atrophic uterine lining). Amenorrhoea occurs in 20% of women using Implanon®.2 However, there is normally a high rate of early miscarriage, mainly due to factors pertaining to the genetic normality of the embryo, and so this is an alternative possibility.  In this patient’s situation she had recommenced ovulation and hence conceived despite her amenorrhoea. Recommencement of ovulation is more likely after 30 months in patients using Implanon®.3

This patient was of normal weight, but the product information offers a warning about the use of Implanon® in overweight women:

“Serum concentrations of etonogestrel are  inversely related to body weight and decrease with time after implant insertion. It is therefore possible that IMPLANON may be less effective in overweight women, especially in the presence 24 of other factors that decrease serum etonogestrel concentrations such as concomitant use of hepatic enzyme inducers.”2

Regarding the risk of pregnancy in women using Implanon® the product information states:

“In the subgroup of women 18 to 35 years of age at entry, 6 pregnancies during 20,648 cycles of use were reported. Two pregnancies occurred in each of Years 1, 2 and 3. Each conception was likely to have occurred shortly before or within 2 weeks after IMPLANON removal. With these 6 pregnancies, the cumulative Pearl Index was 0.38 pregnancies per 100 women-years of use.”2 

 

1. Jones, G. SydPath Information Sheet: hCG (human Chorionic Gonadotrophin),  Department of Chemical Pathology, 4 February 2013
http://www.sydpath.stvincents.com.au/tests/ChemFrames/hCG.htm

2. Merck Sharpe & Dohme, Implanon® Product information, 2016
http://www.merck.com/product/usa/pi_circulars/i/implanon/implanon_pi.pdf
http://www.implanon-usa.com/en/consumer/main/prescribing-information.xhtml

3. Mäkäräinen L. et al. Ovarian function during the use of a single contraceptive implant: Implanon compared with Norplant. Fertility & Sterility. 1998 Apr; 69(4): 714-21.
http://www.ncbi.nlm.nih.gov/pubmed/9548163