Successful pregnancy after in-vitro fertilization and transmyometrial embryo transfer in a patient with congenital atresia of cervix: Case report

Leena Anttila1,3, Tuula-Anneli Penttilä1,2 and Anne-Maria Suikkari1,2

1 Department of Obstetrics and Gynecology, Turku University Central Hospital, Turku, Finland.


    Abstract
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
A case report of a patient with congenital cervical atresia diagnosed at the age of 24 years is given. The attempts to create a neocervix were unsuccessful. Since no signs of retrograde menstruation or haematometra were observed, in agreement with the patient hysterectomy was not performed. At the age of 32 years, a successful pregnancy was achieved after an in-vitro fertilization and transmyometrial embryo transfer. Due to rapidly progressing pre-eclampsia, an elective Caesarean section was performed at 32 weeks gestation. A 1610 g healthy male infant in breech presentation was born. The post-partum period was uneventful.

Key words: cervix/congenital cervical atresia/embryo transfer/IVF/pregnancy


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Congenital cervical atresia with or without the presence of a normal vagina is a rare anomaly of the Müllerian system (Faber and Marchant, 1975Go; Buttram, 1983Go; Rock et al., 1983Go). Two distinct types of anatomical variation have been reported: a complete absence of the cervical stroma or a fibrous cervical cord with islands of endocervical glands (Rock et al., 1983Go). The mechanisms causing disturbed development of the cervix are unknown.

In clinical practice, the aims of treatment of this condition are firstly to relieve the symptoms related to haematometra and retrograde menstruation, and secondly to restore fertility and regular bleedings. Reconstructive operations have been problematic due to severe complications, i.e. intra-abdominal infections, eventually resulting in hysterectomy in most cases (Maciulla et al., 1978Go, Rock et al., 1984Go). Recently it has been suggested that a reconstructive operation may be worthwhile only in cases with cervical dysgenesis, but not with a complete absence of cervix (Jacobsen and DeCherney,1997).

We describe a successful pregnancy in a woman with cervical dysgenesis and hypofunctioning endometrium. The pregnancy was achieved after in-vitro fertilization (IVF) and an ultrasound-guided transmyometrial embryo transfer. To our knowledge this is the first reported case of a successful pregnancy after unsuccessful operative correction of congenital cervical atresia.


    Case report
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
In 1989 a 24-year-old woman was referred to the outpatient clinic of the reproductive endocrinology unit at Turku University Central Hospital for primary amenorrhoea. The onsets of thelarche and pubarche had been normal at 12 years of age. Her height was 150 cm and she weighed 41 kg. Her karyotype was of a normal 46,XX female. On gynaecological examination, a 5 cm long vaginal vault, but no cervix was seen. Ultrasound examination revealed a normal size uterus with thin (4 mm) endometrium and normal ovaries. An intravenous pyelogram and an adrenocorticotropic hormone stimulation test did not indicate any urinary tract anomaly or adrenal dysfunction. Repeated measurements of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol, and progesterone concentrations confirmed a normal ovulatory cycle. A magnetic resonance imaging (MRI) of the pelvis suggested a normal uterus with a short, narrow cervix.

The patient underwent two operations in order to build a functional uterovaginal passage. In January 1990, a colpoplasty was performed, but the attempt to create a canal through the cervical stoma was unsuccessful. Eight months later another attempt to reconstruct the uterovaginal canal was performed by laparotomy. Prior to the operation patient received oestrogen patches (100 µg/day) for 8 weeks in order to grow an endometrial lining and cause haematometra, making it easier to enter the uterine cavity. No endometrial thickening was observed, however. Operative exploration revealed a bicornuate uterus with a rudimentary left horn and a normal right Fallopian tube. Both ovaries were normal and no endometriosis was seen. A connection between the uterine cavity and the vagina was created by placing a rubber catheter through the fibrotic cervical tissue for 3 weeks. Unfortunately, the canal was stenosed 2 months later. Since no signs of haematometra or endometriosis were seen, it was concluded that the endometrium was hypofunctional, possibly due to an oestrogen receptor defect. The patient had not consented to hysterectomy because she felt well and had no menstrual problems.

Five years later in 1994, at the age of 30 years, the patient presented again at the reproductive endocrinology unit, because she wished to become pregnant and have a child. The serum FSH, thyroid-stimulating-hormone, and prolactin concentrations, as well as her partner's semen analysis were normal. The couple was informed of the risks of assisted reproductive techniques and the possible pregnancy. The couple refused the options of adoption and the use of a surrogate mother. A decision to attempt IVF and laparoscopic zygote intra-Fallopian transfer (ZIFT) was made. After pituitary down-regulation with nafarelin (Synarela®, Searle, Södertälje, Sweden), a total dose of 1125 IU of human menopausal gonadotrophin (Humegon®, Organon, Oss, The Netherlands) was used for ovarian stimulation. Ovum retrieval was performed by an ultrasound-guided vaginal puncture of follicles 36 h after i.m. administration of human chorionic gonadotrophin (HCG). Out of the four oocytes retrieved, three fertilized. At laparoscopy for ZIFT the right tube was observed to be occluded. The embryos were frozen at 2- to 4-cell stage, but failed to survive the thaw.

In September 1996, a second IVF cycle was performed using a mid-luteal down-regulation protocol with nafarelin (Synarela®, Searle). For ovarian stimulation 150 IU urinary FSH (Fertinorm HP®, Serono, Randolph, MA, USA) s.c. was used for 11 days. Oocyte retrieval was performed as described above. Five of eight oocytes were fertilized, and two 4-cell stage embryos were selected for ultrasound-guided transmyometrial embryo transfer, which was performed under general anaesthesia using a 6 MHz endovaginal ultrasound probe (Tosbee SSA-240-A, Toshiba, Tokyo, Japan) and a `Towako' embryo transfer catheter (Cook, Sydney, Australia) (Kato et al., 1993Go, Sharif et al., 1996Go). For luteal support daily 600 mg micronized progesterone (Lugesteron®, Leiras, Turku, Finland) was administered vaginally. Fourteen days after the embryo transfer, serum HCG concentration was 588 U/l, and 2 weeks later, vaginal ultrasonography revealed an intrauterine gestational sac with fetal heartbeat.

The pregnancy progressed normally until 24 weeks gestation, when the patient was referred to the antenatal clinic for haematuria. A mild cystitis and bleeding inside the urethra were observed by cystoscopy. A possible invasion of placental tissue into the bladder was excluded by ultrasound, Doppler, and MRI examinations. An urinary infection was treated with pivmecillinamin 200 mgx3/day (Selexid®, Lövens, Ballerup, Denmark).

Three weeks later, the patient was admitted to the antenatal clinic for premature uterine contractions. The well-being of the fetus was monitored by repeated cardiotocography, ultrasound, and Doppler examinations. Since there was a high risk of premature delivery, maturation of fetal lungs was induced at 28 weeks gestation using weekly dexamethasone 8 mg i.m. injections (Dexametason®, Orion, Helsinki, Finland) for 5 weeks. The maturation of fetal lungs was confirmed by the measurement of lecitin/sphingomyelin ratio in amniotic fluid at 28 and 30 weeks gestation. At 31 weeks the patent exhibited symptoms of pre-eclampsia (headache and visual disturbances) with elevated blood pressure and oedema. Intravenous magnesium was administred, and because of rapidly progressing pre-eclampia a Caesarean section was performed a week later. A healthy boy weighing 1610 g was born in breech presentation (Apgar 6/7). The uterine cavity was carefully cleaned of decidua at the caesarean section. To reduce postpartum bleeding the patient received 100 mg medroxyprogesterone acetate i.m. (Depo-Provera®, Upjohn, Kalamazoo, USA). Both the mother and the baby recovered well and the postnatal phase was uneventful. One month after stopping breast feeding the patient was symptomless, and an ultrasound examination revealed a thin (3 mm) endometrium. One year later, the patient referred to the reproductive endocrinology unit, because of abdominal pain. A fluid-filled uterus, 7 cm in longitudinal diameter, was seen at ultrasound examination. The haematometra was successfully drained by a needle aspiration under ultrasound guidance and general anaesthesia. After the procedure, progestin treatment with lynestenol (Orgametril®, Organon) 10 mg daily was started to inhibit the proliferation of endometrium. The patient is currently considering a third IVF treatment.


    Discussion
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Obstructive uterine anomalies usually present with abdominal pain and a pelvic mass at the time of menarche. As our patient did not exhibit such symptoms, the diagnosis of a Müllerian anomaly was delayed. An ultrasound examination revealed a small uterus with a thin endometrium. This finding was confirmed by MRI, which has been suggested as superior to computer tomography in evaluation of Müllerian anomalies (Markham et al., 1987Go, Pellerito et al., 1992Go). No signs suggestive of haematometra were observed by ultrasound or MRI examinations in this case. Moreover, despite normal cyclic fluctuations of serum oestradiol and progesterone concentrations the corresponding proliferative and secretory textures of the endometrium were ultrasonographically undetectable (Grunfeld et al., 1991Go). Furthermore, although endometriosis is commonly associated with obstructive Müllerian anomalies (Olive and Henderson, 1987Go), in our patient endometriosis was not observed at laparotomy. All the above observations support the view that the endometrium of our patient was hypofunctional. Interestingly, however, her endometrium `matured' after the delivery, resulting in the development of haematometra about 1 year after stopping breast feeding.

After operative corrections of cervical atresia, four successful pregnancies have been reported previously (Table IGo) (Zarou et al., 1973Go, Fraser, 1989Go, Hampton et al., 1990Go, Thjissen et al., 1990Go). Two of them started spontaneously after reconstructive operations (Zarou et al., 1973Go, Hampton et al., 1990Go) and one after a prolonged treatment of endometriosis with danazol (Fraser, 1989Go). A patient who became pregnant after a second IVF cycle with ZIFT has been described (Thjissen et al., 1990Go). At the first unsuccessful IVF treatment the authors used transmyometrial embryo transfer, which they described as difficult due to a firm myometrium (Thjissen et al., 1990Go). After the first report of successful transmyometrial embryo transfer using a spinal needle in humans (Parsons et al., 1987Go), the equipment and technique for transmyometrial embryo transfer have been improved (Kato et al. 1993Go). In patients with cervical stenosis, the `Towako method' has resulted in pregnancy rates comparable with those obtained by uncomplicated transcervical embryo transfers (Kato et al., 1993Go, Sharif et al., 1996Go).


View this table:
[in this window]
[in a new window]
 
Table I. Summary of the cases with cervical atresia and successful pregnancy
 
In general, the outcome of the few reported pregnancies in women who have undergone reconstructive surgery of cervical atresia has been good (Table IGo). Our patient developed severe pre-eclampsia at 31 weeks gestation. Her condition deteriorated rapidly and a decision to perform a Caesarean section was made at 32 weeks. In this case, the hypoplastic uterus with an abnormal endometrium could facilitate an impaired invasion of the trophoblast cells resulting in a defective placentation and eventually development of pre-eclampsia (Pijnenborg et al., 1991Go).

In patients with cervical atresia, the chance of a spontaneous pregnancy is reduced even after a successful reconstruction of the genital tract due to severe endometriosis, as well as cervical and tubal factors. However, the development of assisted reproductive techniques can now offer a real possibility of a pregnancy and a child of their own to these patients. Therefore, the patients should be carefully counselled when they present at the time of menarche, and hysterectomy should not be offered as the treatment of choice. In a case with normal endometrium, therapeutic amenorrhoea should be considered.


    Acknowledgments
 
The staff of the outpatient clinic of reproductive endocrinology is thanked for their assistance.


    Notes
 
2 Present address: Family Federation of Finland, Infertility Clinic of Turku, Maariankatu 3 A, FIN-20100 Turku, Finland. Back

3 To whom correspondence should be addressed at: Turku University Central Hospital, Department of Obstetrics and Gynecology, Kiinamyllynk. 4–8, FIN-20520 Turku, Finland Back


    References
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Buttram, V.C. Jr. (1983) Müllerian anomalies and their management. Fertil. Steril., 40, 159–163.[ISI][Medline]

Faber, M. and Marchant, D.J. (1975) Congenital absence of the uterine cervix. Am. J. Obstet. Gynecol., 121, 414–417.[ISI][Medline]

Fraser, I.S. (1989) Successful pregnancy in a patient with congenital partial cervical artesia. Obstet. Gynecol., 74 (suppl), 443–445.[Abstract]

Grunfeld, L., Walker, B., Bergh, P.A. et al. (1991) High-resolution endovaginal ultrasonography of the endometrium: a noninvasive test for endometrial adequacy. Obstet. Gynecol., 78, 200–204.[Abstract]

Hampton, H.L., Meeks, G.R., Bates, G.W. et al. (1990) Pregnancy after successful vaginoplasty and cervical stenting for partial atresia of the cervix. Obstet. Gynecol., 76, 900–901.[Abstract]

Jacobsen, L.J. and DeCherney, A. (1997) Shall we operate on Müllerian defects? Results of conventional and hysteroscopic surgery. Hum. Reprod., 12:1376–1381.[Abstract]

Kato, O., Takatsuka, R. and Asch, R.H. (1993) Transvaginal-transmyometrial embryo transfer: the Towako method; experiences of 104 cases. Fertil. Steril., 59, 51–53.[ISI][Medline]

Maciulla, G.J., Heine, M.W. and Christian C.D. (1978) Functional endometrial tissue with vaginal agenesis. J. Reprod. Med., 21, 373–376.[ISI][Medline]

Markham, S.M., Parmley, T.H., Murphy, A.A., et al. (1987) Cervical agenesis combined with vaginal agenesis diagnosed by magnetic resonance imaging. Fertil. Steril., 48, 143–145.[ISI][Medline]

Olive, D.L. and Henderson, D.Y. (1987) Endometriosis and Müllerian anomalies. Obstet. Gynecol., 69, 412–415.[Abstract]

Parsons, J.H., Bolton, V.N., Wilson, L. et al. (1987) Pregnancies following in vitro fertilization and ultrasound-directed surgical embryo-transfer by periurethral and transvaginal techniques. Fertil. Steril., 43, 245–250.

Pijnenborg, R., Anthony, A., Davey, D.A. et al. (1991) Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br. J. Obstet. Gynaecol., 98, 648–655.[ISI][Medline]

Pellerito, J.S., McCarthy, S.M., Doule, M.B. et al. (1992) Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography. Radiology, 182, 795–800.

Rock, J.A., Reeves, L.A., Retto, H. et al. (1983) Success following vaginal creation for Müllerian agenesis. Fertil. Steril., 39, 809–813.[ISI][Medline]

Rock, J.A., Scflaff, W.D., Zacur, H.A. et al. (1984) The clinical management of congenital absence of the uterine cervix. Int. J. Gynaecol. Obstet., 22, 231–235.[ISI][Medline]

Sharif, K., Afnat, M., Lenton, W. et al. (1996) Transmyometrial embryo transfer after difficult immediate mock transcervical transfer. Fertil. Steril., 65, 1071–1074.[ISI][Medline]

Thjissen, R.F.A., Hollanders, J.M.G., Willemsen, W.N.P. et al. (1990) Successful pregnancy after ZIFT in a patient with congenital cervical atresia. Obstet. Gynecol., 76, 902–904.[Abstract]

Zarou, G.S., Esposito, J.M. and Zarou, D.M. (1973) Pregnancy following the surgical correction of concenital atresia of the cervix. Int. J. Gynecol. Obstet., 11, 143–146.

Submitted on September 2, 1998; accepted on February 4, 1999.