- Email: [email protected]
Examination of changes caused by tubal sterilization in ovarian hormone secretion and uterine and ovarian artery blood flow rates
Contraception 70 (2004) 467 – 473
Original research article
Examination of changes caused by tubal sterilization in ovarian hormone secretion and uterine and ovarian artery blood f low rates Arif Serhan Cevrioglua,*, Bumin Degirmencib, Murat Acarb, Mehmet Yilmazera, Demet Erolc, Ahmet Kahramand, Reha Demirele, Hakan Coksuera a
Department of Obstetrics and Gynecology, School of Medicine, Kocatepe University, 03200 Afyon, Turkey b Department of Radiology, School of Medicine, Kocatepe University, 03200 Afyon, Turkey c Department of Anesthesiology, School of Medicine, Kocatepe University, 03200 Afyon, Turkey d Department of Biochemistry, School of Medicine, Kocatepe University, 03200 Af yon, Turkey e Department of Public Health, School of Medicine, Kocatepe University, 03200 Af yon, Turkey Received 19 April 2004; revised 22 July 2004; accepted 12 August 2004
Abstract Objectives: To examine the changes caused by tubal sterilization ( TS) in ovarian hormone secretion and uterine and ovarian circulation. Design: Tubal sterilization was performed by minilaparotomy and laparoscopy methods in 36 women. Blood samples were taken for hormonal tests on Preoperative Day 3 ( D3) of the menstrual cycle, on Postoperative Days 13 – 15 ( periovulatory period) of the same cycle and on D3 in the 1st and 6th months post-TS. Uterine and ovarian artery blood flow rates of the women were measured on the same days as hormonal tests by transvaginal color Doppler ultrasonography ( TVCDUSG). The control group was composed of 15 volunteers in the same age group who preferred the barrier method and who had the same TVCDUSG and hormonal analyses in the same periods. Results: There was a decrease in the uterine and ovarian artery pulsatility index ( PI) measurements and an increase in serum luteinizing hormone ( LH) and estradiol ( E2) values during the periovulatory period as compared with preoperative and postoperative menstrual measurements in all groups. There was no difference between baseline uterine and ovarian artery PI and serum follicle-stimulating hormone, LH and E2 values and those measured on D3 of the menstrual cycle in the 1st and 6th months post-TS. Conclusions: The 6-month postoperative follow-up of groups that had undergone different TS methods showed no difference in uterine or ovarian artery blood flow rates or ovarian hormone secretion in comparison with baseline values. D 2004 Elsevier Inc. All rights reserved. Keywords: Doppler; Ovary; Ovarian blood flow; Tubal sterilization; Ultrasound; Uterine blood flow
1. Introduction Tubal sterilization ( TS) is a birth control method in wide use throughout the world [1]. Because of surgical and anesthetic advances in recent decades, TS methods can now be applied more easily, rapidly and efficiently. Initially, the procedure was performed by laparotomy and then by minilaparotomy, but the widespread use of laparoscopy in the 1970s further popularized TS procedures [2]. As the number of women undergoing sterilization increased, reports concerning the possible long-term sequelae of the procedure, including menstrual symptoms, hormonal and other physical
* Corresponding author. Tel.: +90 272 213 67 07 x209; fax: +90 272 2113 49 96. E-mail address: [email protected] (A.S. Cevrioglu). 0010-7824/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2004.08.004
characteristics and the risk of hysterectomy after an essentially minor elective procedure started to appear [3 –5]. By adversely affecting ovarian function, sterilization has been hypothesized to cause menstrual abnormalities and hormonal disturbances that characterize the so-called post-tubal ligation syndrome [6,7]. The mechanism for the occurrence of posttubal ligation syndrome has long been a matter of conjecture. It has been hypothesized that the destruction of the fallopian tube reduces the utero-ovarian arterial blood flow in the mesosalpinx, thereby leading to tissue damage to the ovary [7]. In addition, venous drainage may be compromised because venous plexuses are located near the arteries. Theoretically, this procedure may also reduce the gonadotropin signal to the ovary, with resultant impairment of follicular growth and even premature loss of ovarian function, as has been reported in women undergoing hysterectomy with
468
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
ovarian conservation [8]. Moreover, a decrease in the blood supply to the ovaries has been postulated to be the mechanism by which both TS and hysterectomy might protect a woman from ovarian cancer [9]. Besides publications describing the negative effects of TS, there are also studies stating that it caused no increase in menstrual dysfunction, dysmenorrhea or premenstrual stress [10,11]. The reason why conflicting results are obtained from studies on the same topic may be lack of a standard approach in the evaluation of ovarian function after TS. Preliminary information on this matter was based on the results of studies using subjective evaluation methods such as the evaluation of menstrual symptoms and amount of menstrual bleeding only [6]. With advances in laboratory technology, studies that evaluated hormonal status in order to investigate menstrual changes after TS more objectively began to appear. Some studies demonstrated decreased estradiol (E2) levels [7,12], whereas other studies found increased E2 levels [13,14]. However, recent studies carried out in a prospective, randomized and controlled fashion showed no evident relation between TS and ovarian follicular reserve or ovarian dysfunction [11,15]. The development of transvaginal probes involving color Doppler images led to a new refinement of gynecological ultrasound and improved the capacity to study and analyze pelvic blood flow, especially utero-ovarian circulation [16 –18]. By studying uterine and ovarian vascular resistance, investigators were able to evaluate the possibility of an anatomical alteration producing endocrinological consequences or vice versa [19,20]. This study was performed to investigate the changes in uterine and ovarian artery blood flow rates and hormonal tests showing ovarian reserve in women having TS by minilaparotomy (Pomeroy technique) and laparoscopy (bipolar cauterization).
2. Materials and methods 2.1. Study and control groups This study was performed as a randomized, controlled, prospective trial with blind assessment of outcome. Thirtysix women who sought contraceptive counseling at the family planning polyclinic and who chose surgical sterilization after counseling were randomly allocated into minilaparotomy and laparoscopy groups. Randomization of the study group was performed by opening 1 of the 36 previously sealed opaque envelopes (potentially 18 assignments to each procedure). After assignment of the operation type, women were referred to one of the two experienced gynecologists (ASC and MY) who would operate on them for preoperative preparations. None of the participants changed the operation type or operator after the second meeting. Fifteen volunteers who decided to use a barrier method for contraception after counseling and were in a similar age group composed the control group. All the women included in the study were more than 30 years old, were multipara, had delivered by the
vaginal route and had regular menstrual cycles. Women in the TS group had at least two children, and those within the control group had at least one child. Women with hypertension and diabetes, those diagnosed as having thyroid dysfunction and who were taking medication for these reasons, those who smoked and those whose body mass index (BMI) was above 35 were excluded from the study. In addition, women who had used hormonal contraception or an intrauterine device in the previous 3 months, had undergone surgery involving the uterus and adnexa or were diagnosed with pelvic inflammatory disease were not included in the study. Informed consent was obtained from all participants, and the ethical committee of the Afyon Kocatepe University approved the study protocol. Following routine preoperative preparations, the uterine and ovarian artery blood flow rates of women who were to undergo TS were measured by transvaginal color Doppler ultrasonography (TVCDUSG), and blood samples were collected for hormone tests indicating ovarian reserve on Day 3 (D3) of the menstrual cycle, in which they would undergo the procedure (preop). Tubal sterilization was performed 1 day after the end of menses, on Days 6 –8 of the menstrual cycle. TVCDUSG measurements and hormonal tests were repeated on the 7th day postoperation, and a second examination was carried out on Days 13–15 of the same cycle (Postop 1) and on D3 of the menstrual cycle in the third (Postop 2) and fourth examinations (Postop 3), carried out in the 1st and 6th postoperative months. In the control group, TVCDUSG measurements and hormonal tests were performed during the first examination on D3 of the cycle, during the second examination 10 days after the first and during the third and fourth examinations carried out on D3 of the cycles 1 and 6 months later. The length of the last menstrual cycle and the number of bleeding days in all women were recorded at the beginning of the study and at the 6-month visit. 2.2. Sonographic evaluation All Doppler studies were performed by the same investigator (BD) in a quiet room with constant light and at a temperature between 218C and 228C. The patients fasted for at least 2 h before the study and rested in the supine position for 15 min before the measurements were obtained. They were examined in the dorsal lithotomy position with the back elevated 308 above the horizontal plane. All follow-up studies were performed at a similar time of day. The investigator from the Department of Radiology was masked to the operation, and control groups and the gynecologists were masked to the TVCDUSG results. Each woman included in the study was assigned a number by the first author before the laboratory workup began, and the women were followed up by the radiology department according to these numbers. Real-time imaging color Doppler ultrasound (Toshiba Nemio, Tokyo, Japan) with a 5.0-MHz broadband transvaginal probe was used to measure uterine and ovarian
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473 Table 1 Study population characteristics Variable
Minilaparotomy (n = 15)
Laparoscopy (n = 14)
Control (n = 12)
p value
Age BMI* Gravida Para
36.9F3.8 28.3F2.8 3.0F0.9 2.4F0.4
35.8F3.6 27.5F3.1 3.3F0.9 2.5F0.4
33.8F3.5 27.3F2.3 2.5F1.1 1.8F0.7
.110 .612 .179 .054
Values are presented as meanFSD. * BMI: weight (kg)/height (m2).
artery blood flow indices. Before the study, the USG equipment settings (including preprocessing, postprocessing and sampling volume of the Doppler gate) were tested for each uterine and ovarian artery. The same settings then were used on each occasion for all patients. The reproducibility of the Doppler measurements was tested before the study started. The investigator measured the pulsatility index (PI) of the uterine and ovarian arteries in 10 menstruating (D3) women (volunteers) twice, 1 h apart, under the conditions described above. The mean (FSD) PI for uterine and ovarian arteries was 1.41F0.086 and 0.99F0.058, respectively. The intraobserver error of measurement was 6.7% and 5.8% for uterine and ovarian arteries, respectively. Uterine artery Doppler blood flow was measured in the longitudinal plane from the uterine artery’s ascending branch located in the midpoint of the distance between the internal os of the cervix and the uterine fundus. Ovarian blood vessels were visualized within the ovarian stroma away from the ovarian surface or around the preovulatory follicle. After visualization of the blood vessels inside the ovarian stroma, blood flow characteristics were analyzed with pulsed Doppler. The angle of insonation was accommodated to obtain maximum blood flow velocity and quality of pulsed Doppler signals. The lowest color pulsed repetition frequency of 500 Hz with wall filter of 50 –100 Hz was used to achieve an enhanced blood flow image of the ovarian vascularity. For uterine arteries, maximal blood flow velocity measurements were corrected based on the angle between
469
the ultrasound beam and the vessels. The Doppler indices were measured after obtaining at least five similar flow rate waves of satisfactory quality. In order to prevent potential measurement errors, measurements were repeated twice at the sites chosen for the uterus and ovary and the mean values were calculated. Then, mean values of right and left uterine and ovarian artery measurements were obtained, and a single uterine and ovarian measurement value was determined for each examination. During the examination, the PI was calculated on a computer and used as a calculation parameter of the Doppler flow curve. The following formula was used in the Doppler PI measurement [21]: Pulsatility index ¼
Peak systolic frequency shift End diastolic frequency shift Mean
Here, bmeanQ represents the temporal mean Doppler frequency shift over one cardiac cycle. 2.3. Hormonal evaluation To evaluate preoperative and postoperative ovarian functions, levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were measured on the same days as the USG examinations. Hormonal measurements were performed via the chemiluminescence method, with the Advia Centaur automatic immunoassay system using E2, LH and FSH diagnostic kits (Bayer, Tarrytown, NY, USA). The sensitivity of the assays was 0.1 mIU/mL for FSH, 0.3 mIU/mL for LH and 10 pg/mL for E2; the interassay coefficients of variation were 2.7%, 3.1% and 5%, respectively. 2.4. Operation technique All operations were performed on Days 6–8 of the menstrual cycle. All women underwent the procedure under general anesthesia with endotracheal intubation, muscle relaxation and controlled breathing. Sevofluorant (Sevorane
Table 2 Hormonal evaluations before and after TS Group
Hormone
Preop
Postop 1
Postop 2
Postop 3
p value
Minilaparotomy (n = 15) Laparoscopy (n = 14) Control (n = 12) Minilaparotomy Laparoscopy Control Minilaparotomy Laparoscopy Control
FSH (mIU/mL)
7.6F1.5 7.2F1.4 6.7F1.6 7.5F2.1 7.2F2.1 5.8F1.8 54.4F18.4 53.7F15.3 48.7F18.9
8.3F1.8 7.9F2.0 7.5F1.4 14.9F4.9a 14.3F4.7a 16.7F5.9a 113.7F31.8b 107.7F41.9b 143.6F75.3b
8.1F2.3 7.9F1.9 7.3F1.4 7.0F1.9 7.1F2.5 6.3F1.7 56.6F15.2 54.9F23.4 49.5F11.8
7.8F2.7 7.1F2.2 6.9F1.4 6.7F1.2 7.0F1.5 6.1F2.0 53.7F13.7 52.4F17.6 46.1F10.9
.573 .175 .257 .001 .001 .001 .001 .003 .008
LH (mIU/mL)
E2 (pg/mL)
Values are presented as meanFSD. Preop: hormonal analyses performed on serum taken on D3 of the menstrual cycle before the operation. Postop 1: hormonal analyses performed on serum taken in the periovulatory period (Days 13 –15) after the operation. Postop 2: hormonal analyses performed on serum taken on D3 of the first menstrual cycle after the operation. Postop 3: hormonal analyses performed on serum taken on D3 of the menstrual cycle 6 months after the operation. a The difference between Postop 1 LH value and other LH values. b The difference between Postop 1 E2 value and other E2 values.
470
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
Table 3 Uterine and ovarian blood flow characteristics before and after TS Group
Artery
Preop
Postop 1
Postop 2
Postop 3
p value
Minilaparotomy (n = 15) Laparoscopy (n = 14) Control (n = 12) Minilaparotomy Laparoscopy Control
Uterine PI
1.40F0.07 1.41F0.11 1.40F0.07 1.00F0.09 0.98F0.14 0.97F0.19
1.37F0.08 1.36F0.09 1.36F0.06a 0.94F0.14 0.95F0.21 0.92F0.10b
1.43F0.13 1.42F0.14 1.41F0.9 1.00F0.17 1.01F0.23 0.96F0.12
1.42F0.11 1.41F0.12 1.41F0.12 0.99F0.19 0.98F0.19 0.97F0.15
.360 .061 .001 .695 .648 .006
Ovarian PI
Values are presented as meanFSD. Preop: PI measurements obtained on D3 of the menstrual cycle before the operation. Postop 1: PI measurements obtained in the periovulatory period (Days 13 –15) after the operation. Postop 2: PI measurements obtained on D3 of the first menstrual cycle after the operation. Postop 3: PI measurements obtained on D3 of the menstrual cycle 6 months after the operation. a The difference between Postop 1 and other postoperative uterine artery PI measurements. b The difference between Postop 1 and preoperative ovarian artery PI measurements.
Liquid, Abbott, Istanbul, Turkey) was used as an inhalation anesthetic. bPressure-controlled ventilationQ mode was used during the operations to ensure normocarbia and to avoid the vasodilatation effect of hypercarbia [22]. One of the gynecologists (MY) carried out a minilaparotomy, and tubal ligation was performed in accordance with the Pomeroy technique, while the other (ASC) performed laparoscopy and bipolar cauterization [23,24]. In the minilaparotomy, a 3- to 4-cm Pfannenstiel’s incision was made at the suprapubic site, and abdominal layers were opened to allow access to the oviducts. Absorbable suturing material (chromic catgut, no. 2/0, Dogsan, Istanbul, Turkey) was used for tubal ligation by the Pomeroy technique. Laparoscopic pneumoperitoneum was induced by CO2 insufflation with a Verres needle passed through the umbilical incision until the intra-abdominal pressure reached 14 mmHg. Following pneumoperitoneum, umbilical 10-mm trocar and telescope (Karl Storz, Tuttlingen, Germany) entries were made. Then, a 5-mm trocar was inserted from the right suprainguinal region under direct laparoscopic observation. Tubal cauterization and transsection procedures were carried out using Tripolar cutting forceps (Lina Medical, Glostrup, Denmark). Cauterization of the tubal segment was performed with a bipolar cautery (Petas Tibbi Cihazlar, Istanbul, Turkey) set at 40 V and 30 W, for 5–10 s, until the tissue held by the forceps turned white. After that, the tubal lumen was cut into two separate parts by the knife projecting from the Tripolar forceps. Tubal ligation and Table 4 Menstrual characteristics before and after TS Group
Menstrual parameter
Before TS
Six months after TS
p value
Minilaparotomy (n = 15) Laparoscopy (n = 14) Control (n = 12) Minilaparotomy Laparoscopy Control
Menstrual cycle length
28.6F3.9
29.1F3.1
.477
27.5F3.0
28.1F2.5
.365
26.9F2.9 5.2F1.3 5.3F1.7 5.6F1.5
27.7F1.6 4.9F1.2 5.1F1.1 5.7F1.6
.282 .173 .426 .723
Number of days of bleeding
Values are presented as meanFSD.
cauterization procedures were carried out on the isthmic part of the tube, and as many of the vessel structures in the tubal mesosalpinx as possible were preserved. The patients were kept under observation in the clinic for 24 h after the operation to avoid any complication associated with surgery or anesthesia and were then discharged. 2.5. Data analysis The data were analyzed with the Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA), version 10.0. Values are presented as meanFSD. One-way analysis of variance (ANOVA) test was used for simultaneous comparisons of the major characteristics of all groups (Table 1). Repeated measures ANOVA was used to examine statistical differences between the hormonal test results and TVCDUSG measurements obtained at different times for each group. When repeated measures ANOVA showed a statistical difference, pairwise comparisons with Bonferroni correction were used to determine from which parameter the difference arose (Tables 2 and 3). Differences between the length of menstrual cycle and the number of bleeding days per cycle before and after TS were analyzed by pairedsamples t test (Table 4). A p value of b .05 was considered statistically significant. 3. Results Of the 36 women in the study, half underwent tubal ligation by minilaparotomy and the other half by laparoscopy. Fifteen women who used a barrier contraceptive method composed the control group. Of the 51 women in the study and control groups, 10 (19.6%) were excluded from the study for various reasons. It was found during operative exploration that one woman had Stage 3 endometriosis, one had Stage 2 endometriosis and one had periadnexal dense adhesions that might have resulted from previous pelvic inflammation; these patients were excluded from the study. One woman in the control group wanted to become pregnant and stopped using birth control. Six women were omitted from the evaluation because their examinations could not be performed on time. As a result,
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
the study was concluded with 15 women (83%) in the minilaparotomy group, 14 (78%) in the laparoscopy group and 12 (80%) in the control group. No complications developed during the intraoperative and postoperative periods in women who underwent TS. A comparison in terms of age, BMI and fertility showed that there was no statistical difference among the groups (Table 1). No difference was found in the comparison of serum FSH levels measured in the preoperative and postoperative periods among the groups and within each group (Table 2). A comparison of the serum LH values measured in the preoperative and postoperative periods revealed that LH levels in all three groups were higher on Days 13–15 of the cycles than on D3 of the menstrual cycles in preoperative and postoperative examinations ( pb .01). Likewise, E2 levels were higher on Days 13–15 of the menstrual cycles than on D3 in preoperative and postoperative examinations in all three groups (p b.01; Table 2). No statistically significant difference was found among baseline FSH, LH and E2 levels and levels measured on D3 of the menstrual cycle in the 1st and 6th months. Uterine and ovarian artery PI values in the minilaparotomy and laparoscopy groups were lower in the periovulatory period than those in the preoperative and postoperative periods, but the difference did not reach statistically significant levels (Table 3). The uterine artery PI value in the periovulatory (Postop 1) period was statistically significantly lower than that measured on D3 of the menstrual cycle in the 6th month in the control group (p b.01; Table 3). The ovarian artery PI value in the periovulatory (Postop 1) period was also statistically significantly lower than that measured on D3 of the menstrual cycle before the operation in the control group (p b.01). There was no statistically significant difference in terms of uterine and ovarian artery PI measurements among baseline values and values measured on D3 in the 1st- and 6th-month examinations in all three groups. There were no statistically significant changes in the average length of the menstrual cycle or in the length of menstrual bleeding before and after sterilization in any group (Table 4). 4. Discussion It has been postulated that the bpost-tubal ligation syndrome Q characterized by menstrual irregularities, dysmenorrhea and/or premenstrual tension that develops after tubal ligation resulted from changes in ovarian hormone secretion due to disturbances of ovarian vascular circulation [3,25]. The degree of disturbance may be dependent on the sterilization procedure and the amount of destruction in the mesovarium. In a prospective controlled study, Shain et al. [26] compared these effects with three different sterilization procedures. They concluded that bipolar cauterization and Pomeroy ligation resulted in more menstrual irregularities compared with the Fallope ring. However, several studies have failed to confirm these findings [27–29].
471
Currently, the main techniques used to show ovarian function are hormonal tests reflecting ovarian follicular activity and transvaginal ultrasonography. Serum FSH and E2 levels studied on D3 of the menstrual cycle are widely acknowledged to reflect ovarian reserve. Although threshold values vary among centers, it is generally accepted that when the FSH value is below 15 mIU/mL and the E2 value is below 80 pg/mL on D3, an infertile patient’s response to ovulation induction may be favorable [30 –32]. The fact that basal FSH and E2 values of the women in our study and control groups were within the stated limits indicates that the selection of patients was appropriate for evaluating the effects of TS on ovarian reserve (Table 2). Luteinizing hormone and E2 values on Days 13–15 of menstrual cycles in the TS groups were significantly higher than those on D3, suggesting that there was no regression in ovarian function immediately after surgery and that ovarian folliculogenesis followed its normal physiological course. Transvaginal ultrasonography (TVUSG), as well as measurement of ovarian volume and determination of the number and diameter of follicles in the ovary, is also considered a rapid, reliable and economical method for evaluating ovarian reserve [33]. When color Doppler technology was combined with TVUSG, the value of Doppler in assessing ovarian function became a popular research topic. Kupesic and Kurjak [16], who investigated the relation between TVCDUSG measurements of ovarian and uterine artery blood flow rates and follicular development, demonstrated that the least resistance against blood flow in both arteries developed in the periovulatory period and that resistance was higher in early menstrual and late luteal periods. It is reported that estrogen receptors are present in the vessel wall and E2 can initiate the release of nitric oxide, a potent vasodilator [34]. Investigators who studied this topic found that ovarian steroids acted by changing the a-adrenergic receptor density of periarterial sympathetic nerves in susceptible tissues and that estrogen led to vasodilatation, whereas progesterone caused vasoconstriction [35]. In the light of this information, it can be expected that serum E2 that increases in the periovulatory period leads to vasodilatation in ovarian and uterine arteries, thus decreasing vessel resistance. We have seen that uterine and ovarian artery PI values in the periovulatory period were lower than those during the menstrual period (Table 3). The fact that serum E2 levels in the hormone profile followup changed in parallel to the decrease in PI supports the thesis of other investigators. The first investigators in the literature using ovarian and uterine artery color Doppler assessment for ovarian function were Sumiala et al. [36]. They performed 16 laparoscopic TS procedures using a Filshie clip and evaluated the participants with uterine and ovarian artery Doppler measurements before the operation and on the 2nd and 90th postoperative days. They found an increase in resistance of 10% to 20% in uterine and ovarian arteries in the measurements on the 2nd postoperative day. They
472
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
also showed that uterine PI measurements in the 3rd month returned to values obtained before sterilization; however, the local resistance increase in the ovarian arteries persisted. Tiras et al. [37], who performed laparoscopic sterilization by bipolar cauterization in 13 women, found a slight but statistically nonsignificant local increase in ovarian vascular resistance and no change in ovarian hormone levels during the postoperative 3rd month follow-up. Geber and Caetano [38] also conducted Doppler color flow analysis of uterine and ovarian arteries before and 1 month after surgery for TS with the Pomeroy technique. They found no differences between the preoperative and postoperative Doppler measurements from both uterine and ovarian arteries. The major difference between our study and those mentioned above is that we formed a control group in addition to the TS groups in order to be able to compare the subjects in terms of Doppler measurements and hormonal tests. Likewise, although others have investigated the effects of a single sterilization method on ovarian circulation, we compared the effects of TS procedures performed by laparoscopic bipolar cauterization and minilaparotomy Pomeroy techniques. In addition, by obtaining Doppler measurements and performing hormone analyses in the same menstrual cycle after TS and in the periovulatory period, we highlighted the effects brought about by the sterilization procedure on the ovary in the early postoperative period. We used artery branches found in the ovarian medulla, not the ovarian artery in the infundibulopelvic ligament, as other researchers did, in order to investigate sequential changes in the ovarian parenchymal circulation by using color Doppler. Previous studies on this topic showed that intraovarian blood flow in TVCDUSG could be useful in following folliculogenesis [21,39]. Our results suggest that TS procedures carried out by laparoscopy and minilaparotomy did not affect uterine or ovarian blood circulation or ovarian hormonal secretion in the postoperative 6-month follow-up. However, since we had a relatively small number of patients in our study and our follow-up period was only for 6 months in both study groups, we cannot conclude on the basis of these findings that the surgical procedures used have no negative effect on vascular circulation in subsequent time periods. The Collaborative Review of Sterilization, a large prospective multicenter study of female sterilization, evaluated menstrual cycles in 5070 women who had undergone TS [40]. Five years after TS, significant menstrual abnormalities were observed in these women as compared with baseline or 1year postoperative data. In a study of 1802 women having TS and subsequently interviewed, DeStefano et al. [41] found that some TS methods are associated with an increased risk of menstrual disturbances and that it may take more than 2 years for these to become apparent. However, these studies do not suggest any mechanism by which TS could determine the cause of such menstrual disturbances. Verco et al. [42] reported that besides the disturbance of vascular circulation, an endometrial perfusion disorder
caused by uterotubal lumen obstruction could also be responsible for the mechanism by which TS leads to menstrual impairment. They monitored endometrial red blood cell flux with the use of a fiber-optic laser Doppler fluxometry probe placed in the endometrial cavity of women who had undergone TS and compared the findings with those from a control group. They showed that endometrial perfusion increased in menstrual, ovulatory and late secretory phases in women who had undergone TS. However, Verco et al. could not clarify the mechanism by which these findings led to menstrual disturbances. Nevertheless, the supposed mechanism of vascular alteration in the ovarian stroma, followed by hormonal alteration and menstrual disturbances, could not be demonstrated by our study. Neither could we demonstrate vascular alterations in the uterine arteries.
Acknowledgments We thank Prof. Dr. Attila Yildirim for his advice during the planning period of this research. This study was supported by the Afyon Kocatepe University Scientific Research Projects Commission (Project no. 022-Tip-11).
References [1] Church CA, Geller JS. Voluntary female sterilization: number one and growing. Popul Rep C 1990;10:1 – 23. [2] Mosher WD. Contraceptive practices in United States, 1982–1988. Fam Plann Perspect 1990;22:198 – 205. [3] Shy KK, Stergachis A, Grothaus LG, Wagner EH, Hecht J, Anderson G. Tubal sterilization and risk of subsequent hospital admission for menstrual disorders. Am J Obstet Gynecol 1992;16:1698 – 705. [4] Taner C, Hakverdi AU, Erden AC, Satici O. Menstrual disorders and pelvic pain after sterilization. Adv Contracep 1995;11:309 – 15. [5] Goldhaber MK, Armstrong MA, Golditch IM, Sheehe PR, Petitti DB, Friedman GD. Long term risk of hysterectomy among 80,007 sterilized and comparison women at Kaiser Permenante, 1971–1987. Am J Epidemiol 1993;138:508 – 21. [6] Gentile GP, Kaufmann SC, Helbig DW. Is there any evidence for a post-tubal sterilization syndrome? Fertil Steril 1998;69:179 – 86. [7] Cattanach JF, Milne BJ. Post-tubal sterilization problems correlated with ovarian steroidogenesis. Contraception 1988;38:541 – 50. [8] Cooper GS, Thorp JM. FSH levels in relation to hysterectomy and to unilateral oophorectomy. Obstet Gynecol 1999;94:969 – 72. [9] Narod SA, Sun P, Ghadirian P, et al. Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case control study. Lancet 2001;357:1467 – 70. [10] Rulin MC, Davidson AR, Philliber SG, Graves WL, Cushman LF. Long-term effect of tubal sterilization on menstrual indices and pelvic pain. Obstet Gynecol 1993;82:118 – 21. [11] Carmona F, Cristobal P, Casamitjana R, Balasch J. Effect of tubal sterilization on ovarian follicular reserve and function. Am J Obstet Gynecol 2003;189:447 – 52. [12] Rojansky N, Halbreich U. Prevalence and severity of premenstrual changes after tubal sterilization. J Reprod Med 1991;36:551 – 5. [13] Hargrove JT, Abraham GE. Endocrine profile of patients with posttubal-ligation syndrome. J Reprod Med 1981;26:359 – 62. [14] Hakverdi AU, Taner CE, Erden AC, Satici O. Changes in ovarian function after tubal sterilization. Adv Contracep 1994;10:51 – 6.
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473 [15] Timonen S, Tuominen J, Irjala K, Maenpaa J. Ovarian function and regulation of the hypothalamic–pituitary– ovarian axis after tubal sterilization. J Reprod Med 2002;47:131 – 6. [16] Kupesic S, Kurjak A. Uterine and ovarian perfusion during the periovulatory period assessed by transvaginal color Doppler. Fertil Steril 1993;60:439 – 43. [17] Kurjak A, Kupesic-Urek S. Normal and abnormal uterine perfusion. In: Jaffe R, Warsof LS, editors. Color Doppler imaging in obstetrics and gynecology. New York7 McGraw-Hill; 1992. p. 255 – 63. [18] De Ziegler D, Cedars MJ. Doppler: a refinement to standard transvaginal ultrasonography for the gynecologist. Semin Reprod Endocrinol 1992;10:34 – 44. [19] De Ziegler D, Bessis R, Frydman R. Vascular resistance of uterine arteries: physiological effects of estradiol and progesterone. Fertil Steril 1991;55:775 – 8. [20] Zaidi J, Jurkovic D, Campbell S, Pitroff R, McGregor A, Tan SL. Description of circadian rhythm in uterine artery blood flow during the periovulatory period. Hum Reprod 1995;10:1642 – 6. [21] Fleischer AC, Golstein RB, Bruner JP, Worrel JA. Doppler sonography in obstetrics and gynecology. In: Callen PW, editor. Ultrasonography in obstetrics and gynecology. Philadelphia7 WB Saunders; 1994. p. 576 – 601. [22] Joris JL. Anesthesia for laparoscopic surgery. In: Miller RD, editor. Anesthesia. Philadelphia7 Churchill Livingstone; 2000. p. 13 – 20. [23] Wheeless CR. Tubal sterilization. In: Thompson JD, Rock JA, editors. Te Linde’s operative gynecology. Philadelphia7 Lippincott; 1992. p. 343 – 54. [24] Hulka JF, Reich H. Sterilization techniques. In: Hulka JF, Reich H, editors. Textbook of laparoscopy. Philadelphia7 WB Saunders; 1998. p. 139 – 66. [25] Poma PA. Tubal sterilizations and later hospitalizations. J Reprod Med 1980;25:272 – 8. [26] Shain RN, Miller WB, Mitchel GW, Holden AE, Rosenthal M. Menstrual pattern change 1 year after sterilization: results of controlled prospective study. Fertil Steril 1989;52:192 – 203. [27] Rivera R, Gaitan JR, Ruiz R, et al. Menstrual patterns and progesterone circulating levels following different procedures of tubal occlusion. Contraception 1989;40:157 – 69. [28] Sahwi S, Toppozoda M, Kamel M, Anwar MY, Ismail AA. Changes in menstrual blood loss after four methods of tubal sterilization. Contraception 1989;40:387 – 98.
473
[29] DeStefano F, Huezo CM, Peterson HB, Rubin GL, Layde PM, Ory HW. Menstrual changes after tubal sterilization. Obstet Gynecol 1983;62: 673 – 81. [30] Shara FI, Scott RT. Assessment of ovarian reserve and treatment of low responders. Infertil Reprod Med Clin North Am 1997;8:501 – 22. [31] Scott RT, Hoffman GE. Prognostic assessment of ovarian reserve. Fertil Steril 1995;63:1 – 11. [32] Smotrich DB, Widra EA, Gindoff PR, Levy MJ, Hall JL, Stillman RJ. Prognostic value of day 3 estradiol on in vitro fertilization outcome. Fertil Steril 1995;64:1136 – 40. [33] Erdem A, Erdem M, Biberoglu K, Arslan M. Age-related changes in ovarian volume, antral follicle counts and basal FSH in women with normal reproductive health. J Reprod Med 2002;47:835 – 40. [34] Gislard V, Millar V, Van Houte P. Effects of 17-h estradiol on endothelium-dependent responses in the rabbit. J Pharmacol Exp Ther 1988;244:19 – 22. [35] Ford SP, Weber LJ, Stormshak F. Role of estradiol 17-beta and progesterone in regulating constriction of ovine arteries. Biol Reprod 1977;17:480 – 6. [36] Sumiala S, Pirhonen J, Tuominen J, Maenpaa J. Increased uterine and ovarian vascular resistance following Filshie clip sterilization: preliminary findings obtained with color Doppler ultrasonography. J Clin Ultrasound 1995;23:511 – 6. [37] Tiras MB, Noyan V, Ozdemir H, Guner H, Yildiz A, Yildirim M. The changes in ovarian hormone levels and ovarian artery blood flow rate after laparoscopic tubal sterilization. Eur J Obstet Gynecol Reprod Biol 2001;99:219 – 21. [38] Geber S, Caetano JP. Doppler colour flow analysis of uterine and ovarian arteries prior to and after surgery for tubal sterilization: a prospective study. Hum Reprod 1996;11:1195 – 8. [39] Collins WP, Jurkovic D, Bourne TH, Kurjak A, Campbell S. Ovarian morphology, endocrine function and intra-follicular blood flow during periovulatory period. Hum Reprod 1991;6:319 – 24. [40] Wilcox LS, Martinez-Schnell B, Peterson HB, Ware JH, Hughes JM. Menstrual function after tubal sterilization. Am J Epidemiol 1992;135:1368 – 81. [41] DeStefano F, Perlman JA, Peterson HB, Diamond EL. Long term risk of menstrual disturbance after tubal sterilization. Am J Obstet Gynecol 1985;152:835 – 41. [42] Verco CJ, Carati CJ, Gannon BJ. Human endometrial perfusion after tubal occlusion. Hum Reprod 1998;13:445 – 9.
Original research article
Examination of changes caused by tubal sterilization in ovarian hormone secretion and uterine and ovarian artery blood f low rates Arif Serhan Cevrioglua,*, Bumin Degirmencib, Murat Acarb, Mehmet Yilmazera, Demet Erolc, Ahmet Kahramand, Reha Demirele, Hakan Coksuera a
Department of Obstetrics and Gynecology, School of Medicine, Kocatepe University, 03200 Afyon, Turkey b Department of Radiology, School of Medicine, Kocatepe University, 03200 Afyon, Turkey c Department of Anesthesiology, School of Medicine, Kocatepe University, 03200 Afyon, Turkey d Department of Biochemistry, School of Medicine, Kocatepe University, 03200 Af yon, Turkey e Department of Public Health, School of Medicine, Kocatepe University, 03200 Af yon, Turkey Received 19 April 2004; revised 22 July 2004; accepted 12 August 2004
Abstract Objectives: To examine the changes caused by tubal sterilization ( TS) in ovarian hormone secretion and uterine and ovarian circulation. Design: Tubal sterilization was performed by minilaparotomy and laparoscopy methods in 36 women. Blood samples were taken for hormonal tests on Preoperative Day 3 ( D3) of the menstrual cycle, on Postoperative Days 13 – 15 ( periovulatory period) of the same cycle and on D3 in the 1st and 6th months post-TS. Uterine and ovarian artery blood flow rates of the women were measured on the same days as hormonal tests by transvaginal color Doppler ultrasonography ( TVCDUSG). The control group was composed of 15 volunteers in the same age group who preferred the barrier method and who had the same TVCDUSG and hormonal analyses in the same periods. Results: There was a decrease in the uterine and ovarian artery pulsatility index ( PI) measurements and an increase in serum luteinizing hormone ( LH) and estradiol ( E2) values during the periovulatory period as compared with preoperative and postoperative menstrual measurements in all groups. There was no difference between baseline uterine and ovarian artery PI and serum follicle-stimulating hormone, LH and E2 values and those measured on D3 of the menstrual cycle in the 1st and 6th months post-TS. Conclusions: The 6-month postoperative follow-up of groups that had undergone different TS methods showed no difference in uterine or ovarian artery blood flow rates or ovarian hormone secretion in comparison with baseline values. D 2004 Elsevier Inc. All rights reserved. Keywords: Doppler; Ovary; Ovarian blood flow; Tubal sterilization; Ultrasound; Uterine blood flow
1. Introduction Tubal sterilization ( TS) is a birth control method in wide use throughout the world [1]. Because of surgical and anesthetic advances in recent decades, TS methods can now be applied more easily, rapidly and efficiently. Initially, the procedure was performed by laparotomy and then by minilaparotomy, but the widespread use of laparoscopy in the 1970s further popularized TS procedures [2]. As the number of women undergoing sterilization increased, reports concerning the possible long-term sequelae of the procedure, including menstrual symptoms, hormonal and other physical
* Corresponding author. Tel.: +90 272 213 67 07 x209; fax: +90 272 2113 49 96. E-mail address: [email protected] (A.S. Cevrioglu). 0010-7824/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2004.08.004
characteristics and the risk of hysterectomy after an essentially minor elective procedure started to appear [3 –5]. By adversely affecting ovarian function, sterilization has been hypothesized to cause menstrual abnormalities and hormonal disturbances that characterize the so-called post-tubal ligation syndrome [6,7]. The mechanism for the occurrence of posttubal ligation syndrome has long been a matter of conjecture. It has been hypothesized that the destruction of the fallopian tube reduces the utero-ovarian arterial blood flow in the mesosalpinx, thereby leading to tissue damage to the ovary [7]. In addition, venous drainage may be compromised because venous plexuses are located near the arteries. Theoretically, this procedure may also reduce the gonadotropin signal to the ovary, with resultant impairment of follicular growth and even premature loss of ovarian function, as has been reported in women undergoing hysterectomy with
468
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
ovarian conservation [8]. Moreover, a decrease in the blood supply to the ovaries has been postulated to be the mechanism by which both TS and hysterectomy might protect a woman from ovarian cancer [9]. Besides publications describing the negative effects of TS, there are also studies stating that it caused no increase in menstrual dysfunction, dysmenorrhea or premenstrual stress [10,11]. The reason why conflicting results are obtained from studies on the same topic may be lack of a standard approach in the evaluation of ovarian function after TS. Preliminary information on this matter was based on the results of studies using subjective evaluation methods such as the evaluation of menstrual symptoms and amount of menstrual bleeding only [6]. With advances in laboratory technology, studies that evaluated hormonal status in order to investigate menstrual changes after TS more objectively began to appear. Some studies demonstrated decreased estradiol (E2) levels [7,12], whereas other studies found increased E2 levels [13,14]. However, recent studies carried out in a prospective, randomized and controlled fashion showed no evident relation between TS and ovarian follicular reserve or ovarian dysfunction [11,15]. The development of transvaginal probes involving color Doppler images led to a new refinement of gynecological ultrasound and improved the capacity to study and analyze pelvic blood flow, especially utero-ovarian circulation [16 –18]. By studying uterine and ovarian vascular resistance, investigators were able to evaluate the possibility of an anatomical alteration producing endocrinological consequences or vice versa [19,20]. This study was performed to investigate the changes in uterine and ovarian artery blood flow rates and hormonal tests showing ovarian reserve in women having TS by minilaparotomy (Pomeroy technique) and laparoscopy (bipolar cauterization).
2. Materials and methods 2.1. Study and control groups This study was performed as a randomized, controlled, prospective trial with blind assessment of outcome. Thirtysix women who sought contraceptive counseling at the family planning polyclinic and who chose surgical sterilization after counseling were randomly allocated into minilaparotomy and laparoscopy groups. Randomization of the study group was performed by opening 1 of the 36 previously sealed opaque envelopes (potentially 18 assignments to each procedure). After assignment of the operation type, women were referred to one of the two experienced gynecologists (ASC and MY) who would operate on them for preoperative preparations. None of the participants changed the operation type or operator after the second meeting. Fifteen volunteers who decided to use a barrier method for contraception after counseling and were in a similar age group composed the control group. All the women included in the study were more than 30 years old, were multipara, had delivered by the
vaginal route and had regular menstrual cycles. Women in the TS group had at least two children, and those within the control group had at least one child. Women with hypertension and diabetes, those diagnosed as having thyroid dysfunction and who were taking medication for these reasons, those who smoked and those whose body mass index (BMI) was above 35 were excluded from the study. In addition, women who had used hormonal contraception or an intrauterine device in the previous 3 months, had undergone surgery involving the uterus and adnexa or were diagnosed with pelvic inflammatory disease were not included in the study. Informed consent was obtained from all participants, and the ethical committee of the Afyon Kocatepe University approved the study protocol. Following routine preoperative preparations, the uterine and ovarian artery blood flow rates of women who were to undergo TS were measured by transvaginal color Doppler ultrasonography (TVCDUSG), and blood samples were collected for hormone tests indicating ovarian reserve on Day 3 (D3) of the menstrual cycle, in which they would undergo the procedure (preop). Tubal sterilization was performed 1 day after the end of menses, on Days 6 –8 of the menstrual cycle. TVCDUSG measurements and hormonal tests were repeated on the 7th day postoperation, and a second examination was carried out on Days 13–15 of the same cycle (Postop 1) and on D3 of the menstrual cycle in the third (Postop 2) and fourth examinations (Postop 3), carried out in the 1st and 6th postoperative months. In the control group, TVCDUSG measurements and hormonal tests were performed during the first examination on D3 of the cycle, during the second examination 10 days after the first and during the third and fourth examinations carried out on D3 of the cycles 1 and 6 months later. The length of the last menstrual cycle and the number of bleeding days in all women were recorded at the beginning of the study and at the 6-month visit. 2.2. Sonographic evaluation All Doppler studies were performed by the same investigator (BD) in a quiet room with constant light and at a temperature between 218C and 228C. The patients fasted for at least 2 h before the study and rested in the supine position for 15 min before the measurements were obtained. They were examined in the dorsal lithotomy position with the back elevated 308 above the horizontal plane. All follow-up studies were performed at a similar time of day. The investigator from the Department of Radiology was masked to the operation, and control groups and the gynecologists were masked to the TVCDUSG results. Each woman included in the study was assigned a number by the first author before the laboratory workup began, and the women were followed up by the radiology department according to these numbers. Real-time imaging color Doppler ultrasound (Toshiba Nemio, Tokyo, Japan) with a 5.0-MHz broadband transvaginal probe was used to measure uterine and ovarian
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473 Table 1 Study population characteristics Variable
Minilaparotomy (n = 15)
Laparoscopy (n = 14)
Control (n = 12)
p value
Age BMI* Gravida Para
36.9F3.8 28.3F2.8 3.0F0.9 2.4F0.4
35.8F3.6 27.5F3.1 3.3F0.9 2.5F0.4
33.8F3.5 27.3F2.3 2.5F1.1 1.8F0.7
.110 .612 .179 .054
Values are presented as meanFSD. * BMI: weight (kg)/height (m2).
artery blood flow indices. Before the study, the USG equipment settings (including preprocessing, postprocessing and sampling volume of the Doppler gate) were tested for each uterine and ovarian artery. The same settings then were used on each occasion for all patients. The reproducibility of the Doppler measurements was tested before the study started. The investigator measured the pulsatility index (PI) of the uterine and ovarian arteries in 10 menstruating (D3) women (volunteers) twice, 1 h apart, under the conditions described above. The mean (FSD) PI for uterine and ovarian arteries was 1.41F0.086 and 0.99F0.058, respectively. The intraobserver error of measurement was 6.7% and 5.8% for uterine and ovarian arteries, respectively. Uterine artery Doppler blood flow was measured in the longitudinal plane from the uterine artery’s ascending branch located in the midpoint of the distance between the internal os of the cervix and the uterine fundus. Ovarian blood vessels were visualized within the ovarian stroma away from the ovarian surface or around the preovulatory follicle. After visualization of the blood vessels inside the ovarian stroma, blood flow characteristics were analyzed with pulsed Doppler. The angle of insonation was accommodated to obtain maximum blood flow velocity and quality of pulsed Doppler signals. The lowest color pulsed repetition frequency of 500 Hz with wall filter of 50 –100 Hz was used to achieve an enhanced blood flow image of the ovarian vascularity. For uterine arteries, maximal blood flow velocity measurements were corrected based on the angle between
469
the ultrasound beam and the vessels. The Doppler indices were measured after obtaining at least five similar flow rate waves of satisfactory quality. In order to prevent potential measurement errors, measurements were repeated twice at the sites chosen for the uterus and ovary and the mean values were calculated. Then, mean values of right and left uterine and ovarian artery measurements were obtained, and a single uterine and ovarian measurement value was determined for each examination. During the examination, the PI was calculated on a computer and used as a calculation parameter of the Doppler flow curve. The following formula was used in the Doppler PI measurement [21]: Pulsatility index ¼
Peak systolic frequency shift End diastolic frequency shift Mean
Here, bmeanQ represents the temporal mean Doppler frequency shift over one cardiac cycle. 2.3. Hormonal evaluation To evaluate preoperative and postoperative ovarian functions, levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were measured on the same days as the USG examinations. Hormonal measurements were performed via the chemiluminescence method, with the Advia Centaur automatic immunoassay system using E2, LH and FSH diagnostic kits (Bayer, Tarrytown, NY, USA). The sensitivity of the assays was 0.1 mIU/mL for FSH, 0.3 mIU/mL for LH and 10 pg/mL for E2; the interassay coefficients of variation were 2.7%, 3.1% and 5%, respectively. 2.4. Operation technique All operations were performed on Days 6–8 of the menstrual cycle. All women underwent the procedure under general anesthesia with endotracheal intubation, muscle relaxation and controlled breathing. Sevofluorant (Sevorane
Table 2 Hormonal evaluations before and after TS Group
Hormone
Preop
Postop 1
Postop 2
Postop 3
p value
Minilaparotomy (n = 15) Laparoscopy (n = 14) Control (n = 12) Minilaparotomy Laparoscopy Control Minilaparotomy Laparoscopy Control
FSH (mIU/mL)
7.6F1.5 7.2F1.4 6.7F1.6 7.5F2.1 7.2F2.1 5.8F1.8 54.4F18.4 53.7F15.3 48.7F18.9
8.3F1.8 7.9F2.0 7.5F1.4 14.9F4.9a 14.3F4.7a 16.7F5.9a 113.7F31.8b 107.7F41.9b 143.6F75.3b
8.1F2.3 7.9F1.9 7.3F1.4 7.0F1.9 7.1F2.5 6.3F1.7 56.6F15.2 54.9F23.4 49.5F11.8
7.8F2.7 7.1F2.2 6.9F1.4 6.7F1.2 7.0F1.5 6.1F2.0 53.7F13.7 52.4F17.6 46.1F10.9
.573 .175 .257 .001 .001 .001 .001 .003 .008
LH (mIU/mL)
E2 (pg/mL)
Values are presented as meanFSD. Preop: hormonal analyses performed on serum taken on D3 of the menstrual cycle before the operation. Postop 1: hormonal analyses performed on serum taken in the periovulatory period (Days 13 –15) after the operation. Postop 2: hormonal analyses performed on serum taken on D3 of the first menstrual cycle after the operation. Postop 3: hormonal analyses performed on serum taken on D3 of the menstrual cycle 6 months after the operation. a The difference between Postop 1 LH value and other LH values. b The difference between Postop 1 E2 value and other E2 values.
470
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
Table 3 Uterine and ovarian blood flow characteristics before and after TS Group
Artery
Preop
Postop 1
Postop 2
Postop 3
p value
Minilaparotomy (n = 15) Laparoscopy (n = 14) Control (n = 12) Minilaparotomy Laparoscopy Control
Uterine PI
1.40F0.07 1.41F0.11 1.40F0.07 1.00F0.09 0.98F0.14 0.97F0.19
1.37F0.08 1.36F0.09 1.36F0.06a 0.94F0.14 0.95F0.21 0.92F0.10b
1.43F0.13 1.42F0.14 1.41F0.9 1.00F0.17 1.01F0.23 0.96F0.12
1.42F0.11 1.41F0.12 1.41F0.12 0.99F0.19 0.98F0.19 0.97F0.15
.360 .061 .001 .695 .648 .006
Ovarian PI
Values are presented as meanFSD. Preop: PI measurements obtained on D3 of the menstrual cycle before the operation. Postop 1: PI measurements obtained in the periovulatory period (Days 13 –15) after the operation. Postop 2: PI measurements obtained on D3 of the first menstrual cycle after the operation. Postop 3: PI measurements obtained on D3 of the menstrual cycle 6 months after the operation. a The difference between Postop 1 and other postoperative uterine artery PI measurements. b The difference between Postop 1 and preoperative ovarian artery PI measurements.
Liquid, Abbott, Istanbul, Turkey) was used as an inhalation anesthetic. bPressure-controlled ventilationQ mode was used during the operations to ensure normocarbia and to avoid the vasodilatation effect of hypercarbia [22]. One of the gynecologists (MY) carried out a minilaparotomy, and tubal ligation was performed in accordance with the Pomeroy technique, while the other (ASC) performed laparoscopy and bipolar cauterization [23,24]. In the minilaparotomy, a 3- to 4-cm Pfannenstiel’s incision was made at the suprapubic site, and abdominal layers were opened to allow access to the oviducts. Absorbable suturing material (chromic catgut, no. 2/0, Dogsan, Istanbul, Turkey) was used for tubal ligation by the Pomeroy technique. Laparoscopic pneumoperitoneum was induced by CO2 insufflation with a Verres needle passed through the umbilical incision until the intra-abdominal pressure reached 14 mmHg. Following pneumoperitoneum, umbilical 10-mm trocar and telescope (Karl Storz, Tuttlingen, Germany) entries were made. Then, a 5-mm trocar was inserted from the right suprainguinal region under direct laparoscopic observation. Tubal cauterization and transsection procedures were carried out using Tripolar cutting forceps (Lina Medical, Glostrup, Denmark). Cauterization of the tubal segment was performed with a bipolar cautery (Petas Tibbi Cihazlar, Istanbul, Turkey) set at 40 V and 30 W, for 5–10 s, until the tissue held by the forceps turned white. After that, the tubal lumen was cut into two separate parts by the knife projecting from the Tripolar forceps. Tubal ligation and Table 4 Menstrual characteristics before and after TS Group
Menstrual parameter
Before TS
Six months after TS
p value
Minilaparotomy (n = 15) Laparoscopy (n = 14) Control (n = 12) Minilaparotomy Laparoscopy Control
Menstrual cycle length
28.6F3.9
29.1F3.1
.477
27.5F3.0
28.1F2.5
.365
26.9F2.9 5.2F1.3 5.3F1.7 5.6F1.5
27.7F1.6 4.9F1.2 5.1F1.1 5.7F1.6
.282 .173 .426 .723
Number of days of bleeding
Values are presented as meanFSD.
cauterization procedures were carried out on the isthmic part of the tube, and as many of the vessel structures in the tubal mesosalpinx as possible were preserved. The patients were kept under observation in the clinic for 24 h after the operation to avoid any complication associated with surgery or anesthesia and were then discharged. 2.5. Data analysis The data were analyzed with the Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA), version 10.0. Values are presented as meanFSD. One-way analysis of variance (ANOVA) test was used for simultaneous comparisons of the major characteristics of all groups (Table 1). Repeated measures ANOVA was used to examine statistical differences between the hormonal test results and TVCDUSG measurements obtained at different times for each group. When repeated measures ANOVA showed a statistical difference, pairwise comparisons with Bonferroni correction were used to determine from which parameter the difference arose (Tables 2 and 3). Differences between the length of menstrual cycle and the number of bleeding days per cycle before and after TS were analyzed by pairedsamples t test (Table 4). A p value of b .05 was considered statistically significant. 3. Results Of the 36 women in the study, half underwent tubal ligation by minilaparotomy and the other half by laparoscopy. Fifteen women who used a barrier contraceptive method composed the control group. Of the 51 women in the study and control groups, 10 (19.6%) were excluded from the study for various reasons. It was found during operative exploration that one woman had Stage 3 endometriosis, one had Stage 2 endometriosis and one had periadnexal dense adhesions that might have resulted from previous pelvic inflammation; these patients were excluded from the study. One woman in the control group wanted to become pregnant and stopped using birth control. Six women were omitted from the evaluation because their examinations could not be performed on time. As a result,
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
the study was concluded with 15 women (83%) in the minilaparotomy group, 14 (78%) in the laparoscopy group and 12 (80%) in the control group. No complications developed during the intraoperative and postoperative periods in women who underwent TS. A comparison in terms of age, BMI and fertility showed that there was no statistical difference among the groups (Table 1). No difference was found in the comparison of serum FSH levels measured in the preoperative and postoperative periods among the groups and within each group (Table 2). A comparison of the serum LH values measured in the preoperative and postoperative periods revealed that LH levels in all three groups were higher on Days 13–15 of the cycles than on D3 of the menstrual cycles in preoperative and postoperative examinations ( pb .01). Likewise, E2 levels were higher on Days 13–15 of the menstrual cycles than on D3 in preoperative and postoperative examinations in all three groups (p b.01; Table 2). No statistically significant difference was found among baseline FSH, LH and E2 levels and levels measured on D3 of the menstrual cycle in the 1st and 6th months. Uterine and ovarian artery PI values in the minilaparotomy and laparoscopy groups were lower in the periovulatory period than those in the preoperative and postoperative periods, but the difference did not reach statistically significant levels (Table 3). The uterine artery PI value in the periovulatory (Postop 1) period was statistically significantly lower than that measured on D3 of the menstrual cycle in the 6th month in the control group (p b.01; Table 3). The ovarian artery PI value in the periovulatory (Postop 1) period was also statistically significantly lower than that measured on D3 of the menstrual cycle before the operation in the control group (p b.01). There was no statistically significant difference in terms of uterine and ovarian artery PI measurements among baseline values and values measured on D3 in the 1st- and 6th-month examinations in all three groups. There were no statistically significant changes in the average length of the menstrual cycle or in the length of menstrual bleeding before and after sterilization in any group (Table 4). 4. Discussion It has been postulated that the bpost-tubal ligation syndrome Q characterized by menstrual irregularities, dysmenorrhea and/or premenstrual tension that develops after tubal ligation resulted from changes in ovarian hormone secretion due to disturbances of ovarian vascular circulation [3,25]. The degree of disturbance may be dependent on the sterilization procedure and the amount of destruction in the mesovarium. In a prospective controlled study, Shain et al. [26] compared these effects with three different sterilization procedures. They concluded that bipolar cauterization and Pomeroy ligation resulted in more menstrual irregularities compared with the Fallope ring. However, several studies have failed to confirm these findings [27–29].
471
Currently, the main techniques used to show ovarian function are hormonal tests reflecting ovarian follicular activity and transvaginal ultrasonography. Serum FSH and E2 levels studied on D3 of the menstrual cycle are widely acknowledged to reflect ovarian reserve. Although threshold values vary among centers, it is generally accepted that when the FSH value is below 15 mIU/mL and the E2 value is below 80 pg/mL on D3, an infertile patient’s response to ovulation induction may be favorable [30 –32]. The fact that basal FSH and E2 values of the women in our study and control groups were within the stated limits indicates that the selection of patients was appropriate for evaluating the effects of TS on ovarian reserve (Table 2). Luteinizing hormone and E2 values on Days 13–15 of menstrual cycles in the TS groups were significantly higher than those on D3, suggesting that there was no regression in ovarian function immediately after surgery and that ovarian folliculogenesis followed its normal physiological course. Transvaginal ultrasonography (TVUSG), as well as measurement of ovarian volume and determination of the number and diameter of follicles in the ovary, is also considered a rapid, reliable and economical method for evaluating ovarian reserve [33]. When color Doppler technology was combined with TVUSG, the value of Doppler in assessing ovarian function became a popular research topic. Kupesic and Kurjak [16], who investigated the relation between TVCDUSG measurements of ovarian and uterine artery blood flow rates and follicular development, demonstrated that the least resistance against blood flow in both arteries developed in the periovulatory period and that resistance was higher in early menstrual and late luteal periods. It is reported that estrogen receptors are present in the vessel wall and E2 can initiate the release of nitric oxide, a potent vasodilator [34]. Investigators who studied this topic found that ovarian steroids acted by changing the a-adrenergic receptor density of periarterial sympathetic nerves in susceptible tissues and that estrogen led to vasodilatation, whereas progesterone caused vasoconstriction [35]. In the light of this information, it can be expected that serum E2 that increases in the periovulatory period leads to vasodilatation in ovarian and uterine arteries, thus decreasing vessel resistance. We have seen that uterine and ovarian artery PI values in the periovulatory period were lower than those during the menstrual period (Table 3). The fact that serum E2 levels in the hormone profile followup changed in parallel to the decrease in PI supports the thesis of other investigators. The first investigators in the literature using ovarian and uterine artery color Doppler assessment for ovarian function were Sumiala et al. [36]. They performed 16 laparoscopic TS procedures using a Filshie clip and evaluated the participants with uterine and ovarian artery Doppler measurements before the operation and on the 2nd and 90th postoperative days. They found an increase in resistance of 10% to 20% in uterine and ovarian arteries in the measurements on the 2nd postoperative day. They
472
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473
also showed that uterine PI measurements in the 3rd month returned to values obtained before sterilization; however, the local resistance increase in the ovarian arteries persisted. Tiras et al. [37], who performed laparoscopic sterilization by bipolar cauterization in 13 women, found a slight but statistically nonsignificant local increase in ovarian vascular resistance and no change in ovarian hormone levels during the postoperative 3rd month follow-up. Geber and Caetano [38] also conducted Doppler color flow analysis of uterine and ovarian arteries before and 1 month after surgery for TS with the Pomeroy technique. They found no differences between the preoperative and postoperative Doppler measurements from both uterine and ovarian arteries. The major difference between our study and those mentioned above is that we formed a control group in addition to the TS groups in order to be able to compare the subjects in terms of Doppler measurements and hormonal tests. Likewise, although others have investigated the effects of a single sterilization method on ovarian circulation, we compared the effects of TS procedures performed by laparoscopic bipolar cauterization and minilaparotomy Pomeroy techniques. In addition, by obtaining Doppler measurements and performing hormone analyses in the same menstrual cycle after TS and in the periovulatory period, we highlighted the effects brought about by the sterilization procedure on the ovary in the early postoperative period. We used artery branches found in the ovarian medulla, not the ovarian artery in the infundibulopelvic ligament, as other researchers did, in order to investigate sequential changes in the ovarian parenchymal circulation by using color Doppler. Previous studies on this topic showed that intraovarian blood flow in TVCDUSG could be useful in following folliculogenesis [21,39]. Our results suggest that TS procedures carried out by laparoscopy and minilaparotomy did not affect uterine or ovarian blood circulation or ovarian hormonal secretion in the postoperative 6-month follow-up. However, since we had a relatively small number of patients in our study and our follow-up period was only for 6 months in both study groups, we cannot conclude on the basis of these findings that the surgical procedures used have no negative effect on vascular circulation in subsequent time periods. The Collaborative Review of Sterilization, a large prospective multicenter study of female sterilization, evaluated menstrual cycles in 5070 women who had undergone TS [40]. Five years after TS, significant menstrual abnormalities were observed in these women as compared with baseline or 1year postoperative data. In a study of 1802 women having TS and subsequently interviewed, DeStefano et al. [41] found that some TS methods are associated with an increased risk of menstrual disturbances and that it may take more than 2 years for these to become apparent. However, these studies do not suggest any mechanism by which TS could determine the cause of such menstrual disturbances. Verco et al. [42] reported that besides the disturbance of vascular circulation, an endometrial perfusion disorder
caused by uterotubal lumen obstruction could also be responsible for the mechanism by which TS leads to menstrual impairment. They monitored endometrial red blood cell flux with the use of a fiber-optic laser Doppler fluxometry probe placed in the endometrial cavity of women who had undergone TS and compared the findings with those from a control group. They showed that endometrial perfusion increased in menstrual, ovulatory and late secretory phases in women who had undergone TS. However, Verco et al. could not clarify the mechanism by which these findings led to menstrual disturbances. Nevertheless, the supposed mechanism of vascular alteration in the ovarian stroma, followed by hormonal alteration and menstrual disturbances, could not be demonstrated by our study. Neither could we demonstrate vascular alterations in the uterine arteries.
Acknowledgments We thank Prof. Dr. Attila Yildirim for his advice during the planning period of this research. This study was supported by the Afyon Kocatepe University Scientific Research Projects Commission (Project no. 022-Tip-11).
References [1] Church CA, Geller JS. Voluntary female sterilization: number one and growing. Popul Rep C 1990;10:1 – 23. [2] Mosher WD. Contraceptive practices in United States, 1982–1988. Fam Plann Perspect 1990;22:198 – 205. [3] Shy KK, Stergachis A, Grothaus LG, Wagner EH, Hecht J, Anderson G. Tubal sterilization and risk of subsequent hospital admission for menstrual disorders. Am J Obstet Gynecol 1992;16:1698 – 705. [4] Taner C, Hakverdi AU, Erden AC, Satici O. Menstrual disorders and pelvic pain after sterilization. Adv Contracep 1995;11:309 – 15. [5] Goldhaber MK, Armstrong MA, Golditch IM, Sheehe PR, Petitti DB, Friedman GD. Long term risk of hysterectomy among 80,007 sterilized and comparison women at Kaiser Permenante, 1971–1987. Am J Epidemiol 1993;138:508 – 21. [6] Gentile GP, Kaufmann SC, Helbig DW. Is there any evidence for a post-tubal sterilization syndrome? Fertil Steril 1998;69:179 – 86. [7] Cattanach JF, Milne BJ. Post-tubal sterilization problems correlated with ovarian steroidogenesis. Contraception 1988;38:541 – 50. [8] Cooper GS, Thorp JM. FSH levels in relation to hysterectomy and to unilateral oophorectomy. Obstet Gynecol 1999;94:969 – 72. [9] Narod SA, Sun P, Ghadirian P, et al. Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case control study. Lancet 2001;357:1467 – 70. [10] Rulin MC, Davidson AR, Philliber SG, Graves WL, Cushman LF. Long-term effect of tubal sterilization on menstrual indices and pelvic pain. Obstet Gynecol 1993;82:118 – 21. [11] Carmona F, Cristobal P, Casamitjana R, Balasch J. Effect of tubal sterilization on ovarian follicular reserve and function. Am J Obstet Gynecol 2003;189:447 – 52. [12] Rojansky N, Halbreich U. Prevalence and severity of premenstrual changes after tubal sterilization. J Reprod Med 1991;36:551 – 5. [13] Hargrove JT, Abraham GE. Endocrine profile of patients with posttubal-ligation syndrome. J Reprod Med 1981;26:359 – 62. [14] Hakverdi AU, Taner CE, Erden AC, Satici O. Changes in ovarian function after tubal sterilization. Adv Contracep 1994;10:51 – 6.
A.S. Cevrioglu et al. / Contraception 70 (2004) 467– 473 [15] Timonen S, Tuominen J, Irjala K, Maenpaa J. Ovarian function and regulation of the hypothalamic–pituitary– ovarian axis after tubal sterilization. J Reprod Med 2002;47:131 – 6. [16] Kupesic S, Kurjak A. Uterine and ovarian perfusion during the periovulatory period assessed by transvaginal color Doppler. Fertil Steril 1993;60:439 – 43. [17] Kurjak A, Kupesic-Urek S. Normal and abnormal uterine perfusion. In: Jaffe R, Warsof LS, editors. Color Doppler imaging in obstetrics and gynecology. New York7 McGraw-Hill; 1992. p. 255 – 63. [18] De Ziegler D, Cedars MJ. Doppler: a refinement to standard transvaginal ultrasonography for the gynecologist. Semin Reprod Endocrinol 1992;10:34 – 44. [19] De Ziegler D, Bessis R, Frydman R. Vascular resistance of uterine arteries: physiological effects of estradiol and progesterone. Fertil Steril 1991;55:775 – 8. [20] Zaidi J, Jurkovic D, Campbell S, Pitroff R, McGregor A, Tan SL. Description of circadian rhythm in uterine artery blood flow during the periovulatory period. Hum Reprod 1995;10:1642 – 6. [21] Fleischer AC, Golstein RB, Bruner JP, Worrel JA. Doppler sonography in obstetrics and gynecology. In: Callen PW, editor. Ultrasonography in obstetrics and gynecology. Philadelphia7 WB Saunders; 1994. p. 576 – 601. [22] Joris JL. Anesthesia for laparoscopic surgery. In: Miller RD, editor. Anesthesia. Philadelphia7 Churchill Livingstone; 2000. p. 13 – 20. [23] Wheeless CR. Tubal sterilization. In: Thompson JD, Rock JA, editors. Te Linde’s operative gynecology. Philadelphia7 Lippincott; 1992. p. 343 – 54. [24] Hulka JF, Reich H. Sterilization techniques. In: Hulka JF, Reich H, editors. Textbook of laparoscopy. Philadelphia7 WB Saunders; 1998. p. 139 – 66. [25] Poma PA. Tubal sterilizations and later hospitalizations. J Reprod Med 1980;25:272 – 8. [26] Shain RN, Miller WB, Mitchel GW, Holden AE, Rosenthal M. Menstrual pattern change 1 year after sterilization: results of controlled prospective study. Fertil Steril 1989;52:192 – 203. [27] Rivera R, Gaitan JR, Ruiz R, et al. Menstrual patterns and progesterone circulating levels following different procedures of tubal occlusion. Contraception 1989;40:157 – 69. [28] Sahwi S, Toppozoda M, Kamel M, Anwar MY, Ismail AA. Changes in menstrual blood loss after four methods of tubal sterilization. Contraception 1989;40:387 – 98.
473
[29] DeStefano F, Huezo CM, Peterson HB, Rubin GL, Layde PM, Ory HW. Menstrual changes after tubal sterilization. Obstet Gynecol 1983;62: 673 – 81. [30] Shara FI, Scott RT. Assessment of ovarian reserve and treatment of low responders. Infertil Reprod Med Clin North Am 1997;8:501 – 22. [31] Scott RT, Hoffman GE. Prognostic assessment of ovarian reserve. Fertil Steril 1995;63:1 – 11. [32] Smotrich DB, Widra EA, Gindoff PR, Levy MJ, Hall JL, Stillman RJ. Prognostic value of day 3 estradiol on in vitro fertilization outcome. Fertil Steril 1995;64:1136 – 40. [33] Erdem A, Erdem M, Biberoglu K, Arslan M. Age-related changes in ovarian volume, antral follicle counts and basal FSH in women with normal reproductive health. J Reprod Med 2002;47:835 – 40. [34] Gislard V, Millar V, Van Houte P. Effects of 17-h estradiol on endothelium-dependent responses in the rabbit. J Pharmacol Exp Ther 1988;244:19 – 22. [35] Ford SP, Weber LJ, Stormshak F. Role of estradiol 17-beta and progesterone in regulating constriction of ovine arteries. Biol Reprod 1977;17:480 – 6. [36] Sumiala S, Pirhonen J, Tuominen J, Maenpaa J. Increased uterine and ovarian vascular resistance following Filshie clip sterilization: preliminary findings obtained with color Doppler ultrasonography. J Clin Ultrasound 1995;23:511 – 6. [37] Tiras MB, Noyan V, Ozdemir H, Guner H, Yildiz A, Yildirim M. The changes in ovarian hormone levels and ovarian artery blood flow rate after laparoscopic tubal sterilization. Eur J Obstet Gynecol Reprod Biol 2001;99:219 – 21. [38] Geber S, Caetano JP. Doppler colour flow analysis of uterine and ovarian arteries prior to and after surgery for tubal sterilization: a prospective study. Hum Reprod 1996;11:1195 – 8. [39] Collins WP, Jurkovic D, Bourne TH, Kurjak A, Campbell S. Ovarian morphology, endocrine function and intra-follicular blood flow during periovulatory period. Hum Reprod 1991;6:319 – 24. [40] Wilcox LS, Martinez-Schnell B, Peterson HB, Ware JH, Hughes JM. Menstrual function after tubal sterilization. Am J Epidemiol 1992;135:1368 – 81. [41] DeStefano F, Perlman JA, Peterson HB, Diamond EL. Long term risk of menstrual disturbance after tubal sterilization. Am J Obstet Gynecol 1985;152:835 – 41. [42] Verco CJ, Carati CJ, Gannon BJ. Human endometrial perfusion after tubal occlusion. Hum Reprod 1998;13:445 – 9.