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A new approach to treatment of the patients with PCOD
European Journal of Obstetrics & Gynecology and Reproductive Biology 55 (1994) 36-37
A new approach to treatment of the patients with PCOD H. Meden-Vrtovec Department of Obstetrics and Gynecology, University Medical Centre. Slajmerjeva 3, 61000 Ljubljana, Slovenia
1. Introduction
The treatment of the patients with polycystic ovary disease (PCOD) is based on the leading clinical symptoms: infertility, obesity, hirsutism and menstrual disorders. Therapeutic approach in patients with infertility as the main symptom is different from the one applied in patients in whom reproductive function is not the motive for therapy [l]. Several treatment protocols and schedules have therefore been adapted to the patient’s interest; therefore the results of the therapy cannot always be comparable. This is also the case because of different inclusion criteria. Apart from hormonal treatment with gonadotropins, GnRH-analogues and growth-hormone [2], anovulatory infertility has been successfully treated with several surgical procedures 13341. A special diagnostic and therapeutic problem is represented by the group of patients without any evident hormonal or menstrual disorders expressing the typical PCOD reaction only during ovarian stimulation. 2. Materials and methods In the IVF-ET programme in Ljubljana, excessive ovarian reaction to ovarian stimulation was registered in 94 patients between January 1991 and March 1993. Not even one patient had been previously diagnosed with PCOD in its classical form. Average FSH and LH concentration in those patients on Day 7 of untreated cycle was 5.6 f 2.27 IU/ml and 6.19 f 0.35 W/l, respectively, the pattern not corresponding to PCOD. In the course of ovarian stimulation, ultrasound (US) examination revealed the development of multiple ovarian follicles (more than 10 follicles in each ovary). On the day of human chorionic gonadotropin (HCG) administration the average estradiol (E2) concentration was 12.11 f 0.37 nmol/l (nor-
ma1 value for preovulatory follicle being 0.73-2.08 nmol/l - Delfia Reagents Pharmacia). A special treatment protocol was introduced in order to continue the treatment cycle and to avoid the development of ovarian hyperstimulation: 12 h after HCG administration aspiration of all follicles from one ovary was performed, while regular oocyte aspiration from the other ovary took place 36 h after HCG administration (24 h after the first aspiration). Hormonal and clinical parameters were retrospectively evaluated separately for the patients who conceived and for those with failed cycles. 3. Results On average, 17.22 f 3.84 vials of HMG per cycle were used, including the patients treated with GnRHanalogues. At the time of conventional oocyte aspiration the average E, concentration was still very high (8.05 f 0.48 nmol/l) but significantly lower (P = 0.000) than at the time of HCG administration (12.11 f 3.59 nmol/l). On average 6.34 f 3.01 oocytes were retrieved and 2.19 f 1.47 embryos transferred. The comparison of the average FSH concentration in 15 patients who conceived (4.80 IU/l) and in 79 patients who did not (6.00 IU/l) shows no significant differences (P = 0.23); neither do the LH concentration (6.43 and 6.13 IU/ml) and E2 concentration at the time of HCG administration (12.08 and 11.97 nmol/l) and at the time of oocyte retrieval (8.61 and 7.95 nmol/l). A statistically significant difference (P = 0.006) was registered only in the average number of embryos transferred between the patients who conceived (3.13) and those who did not 2.01). 4. Discussion Despite the well-known criteria determining PCOD there are patients in whom the clinical picture develops
OOZS-2243/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved. SSDI 0028-2243(93)01774-N
H. Meden-Vrtovec/
Eur. J. Obstet.
Gynecol.
Reprod.
Biol. 55 (1994)
only in the course of ovarian stimulation. The confrontation with latent or subclinical PCOD becomes obvious with exaggerated E2 levels and multiple follicle development after the treatment has been introduced. Aspiration of ovarian follicles after HCG administration in these cases is the method enabling pregnancy in the treated cycle and the prevention of ovarian hyperstimulation (OHS). The majority of the methods used to prevent OHS are connected with the cancellation of the treatment [5]. None of our patients developed OHS in spite of very high E2 levels and multiple follicles developed in the course of stimulation. Pregnancy rate in the cycles treated with double ovarian aspiration is directly connected with the number of transferred embryos, while high E2 levels seem to have no effect on the outcome of the treatment.
31
36-37
HCG administration followed by the regular oocyte retrieval 36 h after HCG. 3. This type of treatment enables pregnancy in the treated cycle and avoids OHS. None of the patients treated in this way developed OHS, in spite of extremely high E, levels and large multiple ovarian follicles. 4. Pregnancy rate in the treated cycle is directly connected with the number of transferred embryos. 6. References 1
2
5. Conclusions 1. The patients who develop polycystic ovarian reaction with exaggerated Ez concentration in the course of ovarian stimulation without previous hormonal or clinical signs, probably represent a special subclinical or latent form of PCOD. 2. Excessive ovarian reactiveness can be successfully treated with double ovarian aspiration - 12 h after
3
4 5
Meden-Vrtovec H. Theoretical and practical aspects of treating PCOD patients. In: Genazzani AR, Petraglia F, Boselli F, Segre A, Genazzani AD, D’Ambrogio G, eds. Current research in gynecology and obstetrics: diagnostic and therapeutic strategies. Carnforth and New Jersey: Parthenon, 1991; 343-360. Owen EJ, Shoham Z, Mason BA, Ostergaard H, Jacobs HS. Cotreatment with growth hormone after pituitary suppression for ovarian stimulation in in vitro fertilization. Fertil Steril 1991; 56: Suppl 6: 1104-l 110. Mio Y, Toda T, Tanikawa M, Terado H, Harada T, Terakawa N. Transvaginal ultrasound-guided follicular aspiration in the management of anovulatory infertility associated with polycystic ovaries. Fertil Steril 1991; 56: Suppl 6: 1060-1065. Keckstein J. Laparoscopic treatment of polycystic ovary syndrome. Baillieres Clin Obstet Gynaecol 1989; 3: 563-581. Meden-Vrtovec H, Tomazevic T. Severe ovarian hyperstimulation syndrome in the IVF-ET programme. Assist. Reprod. Technol. Androl. 1992; 3: 345-354.
A new approach to treatment of the patients with PCOD H. Meden-Vrtovec Department of Obstetrics and Gynecology, University Medical Centre. Slajmerjeva 3, 61000 Ljubljana, Slovenia
1. Introduction
The treatment of the patients with polycystic ovary disease (PCOD) is based on the leading clinical symptoms: infertility, obesity, hirsutism and menstrual disorders. Therapeutic approach in patients with infertility as the main symptom is different from the one applied in patients in whom reproductive function is not the motive for therapy [l]. Several treatment protocols and schedules have therefore been adapted to the patient’s interest; therefore the results of the therapy cannot always be comparable. This is also the case because of different inclusion criteria. Apart from hormonal treatment with gonadotropins, GnRH-analogues and growth-hormone [2], anovulatory infertility has been successfully treated with several surgical procedures 13341. A special diagnostic and therapeutic problem is represented by the group of patients without any evident hormonal or menstrual disorders expressing the typical PCOD reaction only during ovarian stimulation. 2. Materials and methods In the IVF-ET programme in Ljubljana, excessive ovarian reaction to ovarian stimulation was registered in 94 patients between January 1991 and March 1993. Not even one patient had been previously diagnosed with PCOD in its classical form. Average FSH and LH concentration in those patients on Day 7 of untreated cycle was 5.6 f 2.27 IU/ml and 6.19 f 0.35 W/l, respectively, the pattern not corresponding to PCOD. In the course of ovarian stimulation, ultrasound (US) examination revealed the development of multiple ovarian follicles (more than 10 follicles in each ovary). On the day of human chorionic gonadotropin (HCG) administration the average estradiol (E2) concentration was 12.11 f 0.37 nmol/l (nor-
ma1 value for preovulatory follicle being 0.73-2.08 nmol/l - Delfia Reagents Pharmacia). A special treatment protocol was introduced in order to continue the treatment cycle and to avoid the development of ovarian hyperstimulation: 12 h after HCG administration aspiration of all follicles from one ovary was performed, while regular oocyte aspiration from the other ovary took place 36 h after HCG administration (24 h after the first aspiration). Hormonal and clinical parameters were retrospectively evaluated separately for the patients who conceived and for those with failed cycles. 3. Results On average, 17.22 f 3.84 vials of HMG per cycle were used, including the patients treated with GnRHanalogues. At the time of conventional oocyte aspiration the average E, concentration was still very high (8.05 f 0.48 nmol/l) but significantly lower (P = 0.000) than at the time of HCG administration (12.11 f 3.59 nmol/l). On average 6.34 f 3.01 oocytes were retrieved and 2.19 f 1.47 embryos transferred. The comparison of the average FSH concentration in 15 patients who conceived (4.80 IU/l) and in 79 patients who did not (6.00 IU/l) shows no significant differences (P = 0.23); neither do the LH concentration (6.43 and 6.13 IU/ml) and E2 concentration at the time of HCG administration (12.08 and 11.97 nmol/l) and at the time of oocyte retrieval (8.61 and 7.95 nmol/l). A statistically significant difference (P = 0.006) was registered only in the average number of embryos transferred between the patients who conceived (3.13) and those who did not 2.01). 4. Discussion Despite the well-known criteria determining PCOD there are patients in whom the clinical picture develops
OOZS-2243/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved. SSDI 0028-2243(93)01774-N
H. Meden-Vrtovec/
Eur. J. Obstet.
Gynecol.
Reprod.
Biol. 55 (1994)
only in the course of ovarian stimulation. The confrontation with latent or subclinical PCOD becomes obvious with exaggerated E2 levels and multiple follicle development after the treatment has been introduced. Aspiration of ovarian follicles after HCG administration in these cases is the method enabling pregnancy in the treated cycle and the prevention of ovarian hyperstimulation (OHS). The majority of the methods used to prevent OHS are connected with the cancellation of the treatment [5]. None of our patients developed OHS in spite of very high E2 levels and multiple follicles developed in the course of stimulation. Pregnancy rate in the cycles treated with double ovarian aspiration is directly connected with the number of transferred embryos, while high E2 levels seem to have no effect on the outcome of the treatment.
31
36-37
HCG administration followed by the regular oocyte retrieval 36 h after HCG. 3. This type of treatment enables pregnancy in the treated cycle and avoids OHS. None of the patients treated in this way developed OHS, in spite of extremely high E, levels and large multiple ovarian follicles. 4. Pregnancy rate in the treated cycle is directly connected with the number of transferred embryos. 6. References 1
2
5. Conclusions 1. The patients who develop polycystic ovarian reaction with exaggerated Ez concentration in the course of ovarian stimulation without previous hormonal or clinical signs, probably represent a special subclinical or latent form of PCOD. 2. Excessive ovarian reactiveness can be successfully treated with double ovarian aspiration - 12 h after
3
4 5
Meden-Vrtovec H. Theoretical and practical aspects of treating PCOD patients. In: Genazzani AR, Petraglia F, Boselli F, Segre A, Genazzani AD, D’Ambrogio G, eds. Current research in gynecology and obstetrics: diagnostic and therapeutic strategies. Carnforth and New Jersey: Parthenon, 1991; 343-360. Owen EJ, Shoham Z, Mason BA, Ostergaard H, Jacobs HS. Cotreatment with growth hormone after pituitary suppression for ovarian stimulation in in vitro fertilization. Fertil Steril 1991; 56: Suppl 6: 1104-l 110. Mio Y, Toda T, Tanikawa M, Terado H, Harada T, Terakawa N. Transvaginal ultrasound-guided follicular aspiration in the management of anovulatory infertility associated with polycystic ovaries. Fertil Steril 1991; 56: Suppl 6: 1060-1065. Keckstein J. Laparoscopic treatment of polycystic ovary syndrome. Baillieres Clin Obstet Gynaecol 1989; 3: 563-581. Meden-Vrtovec H, Tomazevic T. Severe ovarian hyperstimulation syndrome in the IVF-ET programme. Assist. Reprod. Technol. Androl. 1992; 3: 345-354.