1 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, 2 CREST, Japan Science and Technology, Kawaguchi and 3 Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Ichihara Hospital, Ichihara, Japan
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Abstract |
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Key words: cervical atresia/GnRH agonist/laparoscopic surgery/pituitary tumour/vaginal agenesis
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Introduction |
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Several kinds of GnRH agonists have became widely used for treatment of sex-steroid-dependent gynaecological disorders such as uterine leiomyomata, endometriosis and adenomyosis. Some cases are treated for years with or without hormonal replacement. Although it is well known that GnRH agonists have a dynamic effect on the pituitary gland, i.e. an initial increase in gonadotrophin secretion followed by a marked suppression attributable to gonadotroph desensitization, their long-term effects on the pituitary gland remain unknown.
Here we report a case of vaginal agenesis combined with a functional uterus which was successfully treated by laparoscopically assisted vaginal reconstruction. The patient was treated with GnRH agonists for a total period of over 5 years when a non-functioning pituitary tumour was detected by brain magnetic resonance imaging (MRI). The tumour decreased in size 6 months after the cessation of GnRH agonists.
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Case report |
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Examination confirmed vaginal agenesis with no vaginal dimple or pouch. Transrectal sonography and pelvic MRI showed a fluid-filled uterus consistent with haematometra and an evident endocervix (Figure 1). An intravenous pyelogram was within normal limits. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) concentrations were within normal limits: 3.1, 2.4, and 10 IU/l respectively. Serum oestradiol and testosterone concentrations were also within normal limits: 40.9 pg/ml and 0.3 ng/ml respectively. Bone mineral density of lumbar vertebrae (L2 to L4) was 1.032 g/cm2, which was 92% of that of a young adult female. Buserelin was prescribed again for 1 month, followed by nafarelin for an additional 6 months; then a brain MRI was performed due to fear of long-term effects of GnRH agonists and this revealed a pituitary tumour of 1 cm in diameter which was suspected to be due to these agents (Figure 2A
). The patient did not complain of headache or visual disturbance. Serum was not checked for excessive secretion of growth hormone.
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The patient was instructed to insert a number 24 Hegar dilator at least once a day for 10 min. Repeat examination 4 weeks after the operation revealed complete epithelialization of the neovagina. At 4 months postoperatively, she experienced non-painful cyclic menses. Six months after the cessation of GnRH agonists, brain MRI showed a decrease in size of the pituitary tumour (Figure 2B).
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Discussion |
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Four patients who were treated by the creation of a fistulous tract between the uterus and a patent vagina have been described (Farber and Marchant, 1976) . Although all four patients established regular menses, two required reoperation. Two cases of vaginoplasty in which uterine/cervical stents were placed to conserve uterine function in women with an absent vagina but an intact uterus have been reported (Maciulla et al., 1978
). Both required hysterectomy and castration after suffering serious infectious morbidity. A communication between the vagina and the uterus in four patients had been established (Geary and Weed, 1973
). Three of these subsequently required hysterectomy and partial oophorectomy. More seriously, the fourth patient in their series died from intra-abdominal abscesses. The high morbidity and high mortality often associated with endeavours to conserve the reproductive tract in these women have made hysterectomy the commonly recommended treatment modality.
Recently, however, reports have suggested that successful canalization procedures can be safely performed in selected cases of cervicalvaginal abnormalities. The first successful pregnancy after McIndoe vaginoplasty and cervical stenting for partial cervical atresia and vaginal agenesis was reported (Hampton et al., 1990). Two anatomical variations of congenital cervical atresia: one in which non-canalized cervical stroma is present with or without scattered endocervical glands and another in which there is complete absence of any cervical tissue have been described (Rock et al., 1984
). They suggested that successful reconstruction is unlikely without the presence of cervical stroma. We believe that cervical stromal tissue was present in our case, because MRI showed a dilated and cystic cervix (Figure 1
). We also believe that her potential fertility was restored by the neovaginoplasty although an intrauterine insemination or an abdominal cerclage during early gestation might be necessary because of cervical hypoplasia as reported (Hampton et al., 1990
).
Surgical reconstruction of the atretic cervix may restore fertility and the perception of health, but hysterectomy may remain the definitive therapeutic modality. Education of the patient and her family, as part of informed consent, is important due to the potential for multiple procedures and eventual hysterectomy.
Several notable features are shown in our case. First, endometriosis was revealed during the reconstructive surgery, as is found in many cases of vaginal agenesis with a functional uterus. Since her first diagnostic laparoscopy revealed no endometriosis and GnRH agonists were continuously prescribed thereafter except during an 11 month period, endometriosis with extensive involvement of the anterior and posterior cul-de-sac must have occurred within a relatively short time. The most likely explanation for endometriosis in our case is the transplantation theory, the most widely accepted among several theories relating to the pathogenesis of endometriosis, in which retrograde menstruation is considered as the aetiology of pelvic endometriosis (Sampson, 1927).
Second, vaginal reconstruction was performed using a combined vaginal and laparoscopic approach. Reconstructive surgery in the pregnant patient reported (Hampton et al., 1990) was performed under laparotomy. To our knowledge, there have been only a few reports of a laparoscopic approach to vaginal reconstruction for vaginal agenesis combined with a functional uterus. Laparoscopic application of the conventional transabdominal Vecchietti's operation has been described (Veronikis et al., 1997
) The laparoscopic Vecchietti procedure was employed to reconstruct a neovagina in a patient with a functional uterus. Our laparoscopically assisted reconstruction of a neovagina avoids the stress of a laparotomy and should decrease the risk of injury to the bladder or rectum during the operation. Moreover, it will certainly give the best results in cases complicated with endometriosis because adhesiolysis and electrocauterization of endometriosis can also be performed during the laparoscopic procedure.
Third, sheets of lyophilized porcine dermal skin were used to line a surgically created neovagina. In the original AbbeMcIndoe procedure (McIndoe and Bannister, 1938), a split-thickness skin graft was used to line a neovagina. Many women are reluctant to have the procedure that will leave a permanent and sometimes painful scar at the donor site. Therefore, several investigators have described modifications of the AbbeMcIndoe procedure, including methods that use human peritoneum (Rothman, 1972
), amnion (Ashworth et al., 1986
), and Interceed Absorbable Adhesion Barrier (Johnson & Johnson Patient Care Inc., New Brunswick, NJ, USA) (Jackson and Rosenblatt, 1994
) rather than skin grafts to line the neovagina. Lyophilized porcine dermal skin is inexpensive, readily available, and widely used for temporary resurfacing of skin defects such as burns and injuries (Bromberg et al., 1965
). We regarded the neovagina as a kind of injury and therefore used the lyophilized skin under informed consent of the patient and her family. Although our case is the first report in which a lyophilized porcine dermal skin was used to line the neovagina and no definite conclusions can be made based on this preliminary case, the results achieved with this patient are encouraging.
Fourth, and of most importance, a non-functioning pituitary tumour was revealed by brain MRI after the administration of GnRH agonists for a total period of over 5 years, and its size was decreased 6 months after the cessation of GnRH agonists (Figure 2). It was reported that hypertrophy and hyperplasia/adenoma of the pituitary were observed in rats after 12 months of treatment with leuprolide acetate, a GnRH agonist. No proliferative changes in the pituitary were observed in dogs, monkeys or mice treated for 2 years, indicating a species-specificity of the pituitary changes caused by the GnRH agonist. Immunostaining of the adenomas revealed that the origin might be gonadotrophin-secreting cells (Chatani et al., 1990
). In the human, however, there has been no report of a pituitary adenoma which has occurred after long-term administration of GnRH agonists. As Hall et al. (1994) reported that about 10% of the normal adult population had pituitary abnormalities on MRI scans that were compatible with the diagnosis of asymptomatic pituitary adenomas (Hall et al., 1994
), it is more likely that, in our case, an incidental pituitary adenoma was stimulated by GnRH agonist administration. Further, there have been several reports of pituitary apoplexy, a rare complication of pituitary adenomas, induced by GnRH agonists (Chanson and Schaison, 1995
; Reznik et al., 1997
). Thus, our present report raises the question whether pituitary MRI should be routinely performed upon patients who need long-term administration of GnRH agonists.
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Acknowledgments |
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Notes |
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References |
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Submitted on April 6, 1999; accepted on July 12, 1999.