Successful pregnancy resulting from in-vitro matured oocytes retrieved at laparoscopic surgery in a patient with polycystic ovary syndrome: Case report

Fritz Nagele,1, Michael O. Sator, Johanna Juza and Johannes C. Huber

Minimal Access Surgery Unit, Division of Gynaecologic Endocrinology and Reproductive Medicine, University Department of Obstetrics and Gynaecology, General Hospital of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Combined laparoscopic retrieval of immature oocytes and ovarian electrocautery represents a new management in patients with polycystic ovary syndrome (PCOS), one of the most prevalent endocrinopathies associated with anovulatory infertility. A 31-year-old para II presented with anovulatory, clomiphene-resistant PCOS, and a 6 year history of infertility. Conventional IVF treatment was abandoned in 1999 when she developed severe ovarian hyperstimulation syndrome (OHSS) following gonadotrophin stimulation. Sixteen oocytes were aspirated from both ovaries and collected in culture tubes containing a maturation medium. A total of three 2-cell embryos were transferred 48 h after ICSI. Two weeks after embryo transfer the urinary pregnancy test was positive and after another 2 weeks an ongoing singleton pregnancy with a fetal heartbeat was confirmed at transvaginal ultrasound examination. The combination of laparoscopy, in-vitro maturation and ICSI may open up new therapeutic strategies, even in patients without PCOS and regular menstrual cycles, undergoing laparoscopy for other causes of infertility such as tubal factors and endometriosis.

Key words: in-vitro maturation/laparoscopy/polycystic ovary syndrome


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Polycystic ovary syndrome (PCOS) represents one of the most prevalent endocrinopathies associated with hyperandrogenism and anovulatory infertility. Clinical symptoms include obesity, hirsutism, acne and menstrual disorders, and biochemical manifestations include elevated levels of androgens, LH and the LH/FSH ratio, and reduced concentrations of sex hormone-binding globulin (SHBG). The most typical feature, however, is enlarged ovaries with a hyperechogenic central stroma surrounded by a chain of small subcapsular cysts, as assessed by transvaginal sonography (Franks, 1995Go; Homburg, 1996Go).

Anovulation and infertility are the predominant problems in the majority of women with PCOS, and this explains why the principal aim of different treatment protocols is restoring ovulation. Medical regimens such as clomiphene citrate and conventional high-dose gonadotrophins are often unsuccessful and accompanied by a high prevalence of ovarian hyperstimulation syndrome (OHSS). In this clinical situation, laparoscopic ovarian drilling using monopolar current has been proven to be highly successful, resulting in ovulation rates of up to 90% (Gjonnaes, 1994Go). Another fascinating approach has reported successful pregnancies achieved from in-vitro matured (IVM) oocytes retrieved transvaginally from unstimulated, anovulatory patients with PCOS (Chian et al., 1999Go).


    Case report
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 31-year-old para II presented with anovulatory, clomiphene-resistant PCOS (LH/FSH ratio >2), and a 6 year history of infertility. She had undergone laparoscopic surgery in 1991 (left ovarian cyst), 1993 (left ovarian wedge resection) and 1997 (tubal reconstructive surgery), and her clinical symptoms included obesity (BMI >28), hirsutism, hyperandrogenism, and irregular menstrual cycles. Conventional IVF treatment was abandoned in 1999 when she developed a severe OHSS following gonadotrophin stimulation.

To initiate the IVM treatment cycle, she was given 10 mg dydrogesterone (Duphaston; Solvay Duphar BV., Weesp, Holland) twice daily for 10 days to get a regular menstrual cycle. Following withdrawal uterine bleeding, a complete hormone profile was taken on day 3 (LH: 13.8mU/ml; FSH: 6.0 mU/ml; androstenedione: 5.66 ng/ml; testosterone: 0.92 ng/ml; estradiol: 38 pg/ml; progesterone: 0.39 ng/ml; prolactin: 9.8 ng/ml), and baseline transvaginal ultrasonography (right ovary with 12 follicles, all <6 mm in diameter; left ovary with 15 follicles, all <6 mm in diameter) was performed. Scans were repeated on day 6 (right ovary with 12 follicles, all <7 mm in diameter; left ovary with 14 follicles, all <6 mm in diameter), day 8 (right ovary with 12 follicles, all <7mm in diameter; left ovary with 14 follicles, all <7 mm in diameter) and day 10 (right ovary with 12 follicles, all <8 mm in diameter; left ovary with 14 follicles, all <7 mm in diameter) to exclude the development of the dominant follicle. On day 12 the patient was given 10 000 IU HCG (Pregnyl; Organon, Oss, Holland), and laparoscopy was performed 35 h later (day 14). Immature oocytes were aspirated using a specially designed needle (Cook IVF, Queensland, Australia) placed in the middle of the lower abdomen. Subsequently, ovarian electrocautery was carried out using a monopolar needle (40 watts) at the puncture sites of oocyte retrieval. Sixteen oocytes were aspirated from both ovaries and collected in 10 ml culture tubes (Falcon, Franklin Lakes, NJ, USA) containing a maturation medium [diluted mixture Medi-Cult universal IVF medium (Medi-Cult, Jyllinge, Denmark)] plus 75 IU HMG per 10 ml (Menogon; Ferring, Kiel, Germany). Grouped oocytes were cultured as cumulus cells in Nunc 4-well dishes, 0.5 ml maturation medium per well (without oil) for 24 h. Eleven oocytes reached metaphase II, one oocyte reached metaphase I, four oocytes were degenerated, and routine ICSI was performed on each. Fertilization of seven oocytes (64%) was assessed 16 h later by the appearance of two distinct pronuclei and two polar bodies. A total of three 2-cell embryos were transferred 48 h after ICSI, and the remaining four embryos were cryopreserved. For endometrial preparation and luteal support, the patient received one daily dose of 2 mg estradiol (Progynova; Schering, Berlin, Germany) starting at the day of oocyte retrieval and 400 mg of progesterone administered vaginally starting at the day of ICSI respectively.

Two weeks after the embryo transfer the urinary pregnancy test was positive and after another 2 weeks the serum ß-HCG level was 3850 IU/ml, and an ongoing singleton pregnancy with a fetal heartbeat was confirmed at transvaginal ultrasound examination. In October 2000 the patient had a normal vaginal delivery, the female baby weighing 3180 g. Of note, to date (April 2001) the patient has had two regular menstrual cycles, a recent transvaginal ultrasound revealed completely normal ovaries, and the hormonal profile showed no abnormalities compared with the pre-operative findings.


    Discussion
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
As far as we are aware, this is the first report in the literature of a successful pregnancy resulting from a combined management of laparoscopic retrieval of immature oocytes and concomitant ovarian electrocautery, followed by IVM of the oocytes and fertilization (IVM/IVF). This new treatment regimen potentially offers a number of significant advantages in the management of PCOS, by-passing the well known problems associated with medical ovulation induction. No need for ovarian stimulation clearly means that there are no longer clomiphene failures, and patients can thus be spared administration of supraphysiological doses of gonadotrophins such as FSH—consequently there is no risk of the development of OHSS. Because physical stress with laparoscopy is low and post-operative recovery is quick, pregnancy by ICSI and embryo transfer can be achieved in the same cycle, as shown in this patient. If no pregnancy occurs, cryopreserved embryos can be utilized at a second attempt, provided there are a reasonable number of fertilized oocytes. Finally, if assisted reproduction fails completely, there is still a chance to conceive naturally due to the benefits of laparoscopic surgery in restoring ovulation. In conclusion, the combination of laparoscopy, IVM and ICSI may open up new therapeutic strategies, even in patients without PCOS and regular menstrual cycles, undergoing laparoscopy for other causes of infertility such as tubal factors, peritoneal factors and endometriosis (Mikkelsen et al., 1999Go).


    Notes
 
1 To whom correspondence should be addressed. E-mail: fritz.nagele{at}akh-wien.ac.at Back

Submitted on January 1, 2001; resubmitted on June 8, 2001


    References
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Chian, R.C., Buckett, W.M., Too, L.L. et al. (1999) Pregnancies resulting from in-vitro matured oocytes retrieved from patients with polycystic ovary syndrome after priming with human chorionic gonadotropin. Fertil. Steril., 72, 639–642.[ISI][Medline]

Franks, S. (1995) Polycystic ovary syndrome. N. Engl. J. Med., 333, 853–861.[Free Full Text]

Gjonnaes, H. (1994) Ovarian electrocautery in the treatment of women with polycystic ovary syndrome (PCOS). Acta Obstet. Gynecol. Scand., 73, 407–412.[ISI][Medline]

Homburg, R. (1996) Polycystic ovary syndrome—from gynaecological curiosity to multisystem endocrinopathy. Hum. Reprod., 11, 29–39.[Abstract]

Mikkelsen, A.L., Smith, S.D. and Lindenberg, S. (1999) In-vitro maturation of human oocytes from regularly menstruating women may be successful without follicle stimulating hormone priming. Hum. Reprod., 14, 1847–1851.[Abstract/Free Full Text]

accepted on October 8, 2001.