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EARLY PREGNANCY: Biology and Medicine Editor-in-Chief: Eytan R. Barnea MD, FACOG

April 2001
Volume V, Number 2
ISSN: 1537-6583
Pages: 144-148

Early Pregnancy Is Elusive And Robust

ESS. AL-Mizyen Specialist IVF Registrar, C.G.W. Barnick Consultant Gynaecologist, J.G. Grudzinskas Professor

Department of Obstetrics & Gynaecology, St Bartholomew’s & The Royal London School of Medicine & Dentistry, Royal London Hospital, London, E1 1BB

Key words: Polycystic ovary syndrome; clomiphene citrate resistant; ovarian diathermy

Abstract

Objective
We describe a live birth occurring following bilateral ovarian diathermy, hysteroscopy and dye test in women with clomiphene citrate resistant polycystic ovarian syndrome performed inadvertently during early pregnancy.

Patient(s) and Method(s)
A woman with polycystic ovarian syndrome resistant to Clomiphene citrate had bilateral laparoscopic ovarian diathermy performed inadvertently during early pregnancy. The patient was treated by Clomiphene citrate for 12 cycles then she had bilateral laparoscopic ovarian diathermy and hysteroscopy and dye test. Pelvic ultrasound examination, serum ß hCG, serum LH, FSH, Prolactin, T, SHBG, DHAS and serum E₂ level.

Result(s)
Successful outcome of pregnancy following bilateral laparoscopic ovarian diathermy and hysteroscopy and dye test inadvertently performed during early pregnancy.

Conclusion(s)
That all women scheduled for elective pelvic surgery should be advised to use effective contraception or avoid unprotected sexual intercourse in the preceding month as well as having an hCG test prior to surgery to exclude pregnancy.

Introduction

Polycystic ovary syndrome (PCOS) is the most common problem encountered in reproductive endocrinology. Laparoscopic ovarian diathermy has been reported to be a successful procedure leading to spontaneous ovulation which may be sustained for over 10 years in women with clomiphene citrate resistant PCOS (Gjonnaess,1998). The precise mechanism of action is unclear but it appears that injury to the ovaries triggers ovulation through an alteration of ovarian-pituitary feedback or due to local effects on the ovaries (Ben-SchIomo et al., 1989). Alternatively, one could consider the two hypotheses formulated (Cohen and Leal, 1983); (i) the burning of the ovary provokes a secondary hyperemia, inducing an increase in gonadotrophin concentrations by disrupting the surface unity of the ovary; and (ii) electrocoagulation stimulates the ovarian nerves which transmit excitatory impulses to the superior centres. It is also possible that drainage of androgens and inhibin from the surface follicles could prevent the excessive collagenisation of overlaying ovarian cortex and facilitate a softening of the ovarian tunica. Neighbouring follicles that are not undergoing atresia may then mature and gain access to the ovarian surface, facilitating normal ovulation (Cohen and Audebert, 1989). As adhesions have been reported in 30-40% of women following bilateral ovarian diathermy (Gurgan et al., 1991), we have undertaken a prospective randomised study comparing the effect of unilateral vs bilateral ovarian diathermy. During the conduct of this study, we encountered a case of successful pregnancy outcome following bilateral laparoscopic ovarian diathermy (LOD), hysteroscopy and dye test performed inadvertently during or immediately after implantation.

Patient(s) and Method (s)

A 29 year old woman presented with secondary infertility of three years duration due to chronic anovulation caused by polycystic ovarian syndrome (PCOS) with irregular menstruation occurring every 3-6 months. Transvaginal ultrasound examination revealed an anteverted normal sized uterus, both ovaries being bulky and multicystic with a classical appearance of PCOS, namely more than ten follicles of 3-8mm in diameter and an increase in stromal density (Adams et al .,1985). The diagnosis of PCOS was made, based on clinical, ultrasound and endocrine [serum luteinising hormone (LH) = 12.2 IU, follicle stimulating hormone (FSH)=6.0 IU] findings (Table). Prior to referral to our centre the patient had previously undergone 12 cycles of clomiphene citrate treatment with a maximum dose of 150mg per day for five days which had proved unsuccessful in inducing ovulation. Recently, she had been diagnosed to be a non-insulin dependent diabetic. In April 1998, the patient was admitted for laparoscopic ovarian diathermy (LOD), her last menstrual period being 26 weeks previously. A urinary pregnancy test [detection limit for human chorionic gonadotrophin (hCG) 50mIU/ml, 3rd International hCG Standard] performed on admission was negative on the day of operation and the patient underwent bilateral laparoscopic ovarian diathermy (Gjonnaess,1998), hysteroscopy and tubal patency dye test. Blood samples drawn before the operation, 24 hours post-operatively and one week later, showed a fall in serum LH, FSH levels after a week, no change in serum progesterone (P) but a rise in serum oestradiol (E₂), prolactin, testosterone (T), dehydroepiandrostenediane sulphate (DHAS) and sex hormone binding globulin (SHBG) levels (Table).

Results

At follow-up one week post-operatively, an ultrasound examination revealed a single gestational sac 5.6mm x 4.4mm in the uterus. The serum b hCG level assayed retrospectively on the blood samples collected prior to operation on 7 April, 1998, 24 hours post-operatively on 8 April, 1998 and one week later on 16 April, 1998 were 29 IU, 39 IU and 1615 IU. Repeat ultrasound examination on 23 April, 1998 showed a single viable embryo in the uterus. After regular attendance at the antenatal clinic and an uneventful pregnancy, a live male, small for dates, infant weighing 2.268kg was delivered vaginally at 37 weeks gestation (11 December, 1998). The infant was bottle fed and spontaneous regular menstruation resumed eight weeks later on 4 February, 1999, occurring at 28-35 days intervals. Scan evidence of follicular development and hormonal evidence of ovulation (luteal phase progesterone 36 nmol/l) was observed in April 1999, three months post-partum. A treatment independent pregnancy was diagnosed in August 1999.

Discussion

Early pregnancy is elusive and its diagnosis may be difficult as evidenced here by it being missed firstly by a sensitive urinary test for the detection of hCG and secondly an apparently normal uterine cavity at hysteroscopy and no evidence of a corpus luteum at laparoscopy performed by a very experienced endoscopic surgeon.

The robust nature of the processes of early pregnancy are demonstrated here in that they were all not disrupted by the surgery to the ovarian stroma, the hysteroscopic examination which used saline for distension of the uterine cavity, and the tubal chromopertubation patency test. Whereas successful pregnancy outcome of conceptions occurring in cycles during which invasive procedures such as hysterosalpingography, laparoscopy and chromopertubation, have been reported (Justesen et al., 1987; Yazdi and Rahimi, 1995; Mackey et al., 1971l; Opsahl, 1994), to our knowledge, this is the first report of normal pregnancy progress and outcome following bilateral ovarian diathermy in a conception cycle. Extra care would always be taken if pelvic or adnexal surgery was performed in recognised early pregnancy but, in this situation, the LOD which was performed was bilateral and clearly extensive, as the patient commenced ovulating two months postpartum and conceived again spontaneously within eight months. It is routine practice to perform a sensitive urine pregnancy test in all women undergoing surgery in particular to the pelvis, but inevitably, the diagnosis is missed because the test is performed just prior to implantation or early enough after implantation before there is a sufficient hCG synthesis to be detected by a urinary test. An extensive literature search has failed to reveal much information on this subject although the authors feel that this situation is not an uncommon occurrence, usually leading to a sense of relief by the gynaecologist when the pregnancy, which declares itself later, proceeds to a successful outcome, rather than to the production of a case report such as this.

The authors would like to hear of more of these "near misses", if this is in fact the case. If it is not, then all women scheduled for elective pelvic surgery should be advised to use effective contraception or avoid unprotected sexual intercourse in the preceding month as well as having an hCG test prior to surgery to exclude pregnancy.

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References

Adams, J., Franks, S., Polson, D.W. (1985) Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet., 11, 1375-1379

Ben-Shlomo, I., Homburg, R . and Shalev, E. (1998) Hyperandrogenic anovulation (the polycystic ovary syndrome) - back to the ovary? Hum Reprod .,4, 296-300

Cohen, J..and Audebert , A. (1989) De la mecanique au fonctionnel: place des traitements chirurgicaux endoscopique des dystrophies ovariennes. Edition Masson, Paris, pp 183-194

Cohen, J. and Leal De Meirelles, H. (1983) Fertilite’ apres biopsie ovarienne percoelioscopique. A propos de 477 cas en sterilite. J Gynecol Obstet Bio Reprod., 12, 73-79

Gjonnaess, H. (1998) Late endocrine effects of ovarian electrocautery in women with polycystic ovary syndrome. Fertil Steril., 69, 697-701.

Gurgan, T., Kisnisc,i H.,Yarali, H., Develioglu, O., Zeyenloglu,H., Aksu ,T. (1991) Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease. Fertil Steril., 56, 1176-1178

Justesen, P ., Andersen, PE. Jr.,Rasmussen , F. (1987) Unique etiology of tubal ectopic pregnancy. Acta Obstet Gynecol Scand .,66, 185-186

Mackey, RA.,Glass, RH., Olsen, LE., Vaidya ,R. (1971)Pregnancy following hysterosalingography with oil and water soluble dye. Fertil Steril., 22, 504-507

Opsahl ,M S. (1994) Outcome of pregnancy after laparoscopy and chromotubation during cycles of conception: a report of three cases. Obstet Gynecol .,83, 902-903

Yazdi, G and Rahimi, M. (1994) Term uneventful pregnancies after laparoscopy with chromotubation during cycles of conception. J Amer Assoc Gynecol Laparoscopists ., 2 (supplement 4) S61

Table

Endocrine measurements in early pregnancy outcome, before and subsequently, during bilateral laparoscopic ovarian diathermy and hysteroscopy and dye test on 7 April, 1998. A live embryo has been seen at ultrasound on 14 May 1998.