The use of misoprostol prior to hysteroscopy in postmenopausal women.

BACKGROUND: This study examined whether oral misoprostol exerted a cervical priming effect in postmenopausal women prior to hysteroscopy. METHOD: Thirty-seven patients were randomized to receive either oral misoprostol (400 microg) or placebo (vitamin B(6)) 12 h prior to hysteroscopy. The resistance of the cervix to dilatation was objectively assessed by a cervical tonometer. RESULTS: The mean baseline cervical dilatation (4.2 mm in misoprostol group versus 4.4 mm in placebo group) was similar between the two groups. The mean cumulative force measured (27.7 N in misoprostol group versus 21.8 N in placebo group) was also comparable. None of the patients suffered from any significant side-effects. CONCLUSIONS: These data showed that there were no significant benefits from giving misoprostol pre-operatively in postmenopausal women, and it was concluded that oral misoprostol had no significant cervical priming effect in postmenopausal women.     

Cervical priming prior to operative hysteroscopy: a randomized comparison of laminaria versus misoprostol

BACKGROUND: We aimed to compare efficacy of intravaginal misoprostol versus endocervical laminaria tents prior to operative hysteroscopy in selected cases. METHODS: A total of 144 patients with diagnosed intrauterine lesions scheduled for operative hysteroscopy were randomly allocated to two groups according to method of cervical priming prior to the procedure. Misoprostol 200 microg was inserted into the posterior fornix of the vagina for patients in group A (n=72), while laminaria tents were inserted intracervically in group B patients (n=72). RESULTS: Both methods were effective for cervical dilatation with a mean cervical diameter of 7.5+/-1.2 and 7.6+/-1.2 mm respectively. There was no significant difference in the mean cervical diameter or the time required for cervical dilatation (51.6 versus 51.4 s respectively). In contrast, there was a significant difference between the groups with respect to the insertion difficulty and in doctors' and patients' assessments of the procedure. CONCLUSIONS: Both misoprostol and laminaria were equally effective in inducing proper cervical priming prior to operative hysteroscopy with minimal time of cervical dilatation. Nevertheless, misoprostol may be superior due to easy application, reduced cost, and patient convenience and acceptability.     

The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial.

Misoprostol is effective for cervical priming prior to vacuum aspiration for first trimester termination of pregnancy. Previous studies showed that the oral route was more acceptable to patients but there were higher incidences of side-effects when compared with the vaginal route. This study is to determine the optimal dosage and route of administration of misoprostol for pre-operative cervical dilatation. A double-blind, randomized trial was undertaken for 225 nulliparous women with 8-12 weeks amenorrhoea. They were randomly assigned to groups given 0 (placebo), 200 or 400 microg oral or vaginal misoprostol 3 h prior to vacuum aspiration. In misoprostol-treated groups the baseline cervical dilatation was significantly increased when compared with the placebo group; the effect was dose-related in the oral but not in the vaginal group. The cumulative force and blood loss was significantly decreased in the misoprostol-treated groups. The incidences of side-effects were more frequent in misoprostol groups but were not related to the route and dosage of medication. The duration of procedure, incidences of post-operative complications, the duration of post-operative bleeding and the interval to the first period were similar in the five treatment groups. We conclude that a 3 h pre-treatment interval is effective for both oral and vaginal routes. When given orally, 400 microg is more effective than 200 microg. The efficacy was otherwise similar when compared with the vaginal route. We recommend 400 microg oral misoprostol 3 h prior to vacuum aspiration for cervical dilatation.     

Pregnancy: Oral misoprostol versus placebo for cervical dilatation before vacuum aspiration in first trimester pregnancy

Intravaginal misoprostol has been shown to be effective forcervical priming before a surgically induced abortion. The objectivewas to investigate the effectiveness of oral misoprostol incervical dilatation prior to vacuum aspiration between the 6thand 12th weeks of pregnancy. The results showed that in nulliparouspatients, the median cervical dilatation in the treatment group(7.8 mm) was significantly greater than that in the placebogroup (3.7 mm). In multiparous patients, the difference wasalso statistically significant (9.8 versus 6.0 mm). The easeof dilatation, assessed subjectively by the operating surgeons,was significantly improved in the treatment group. There wasalso a significant reduction in the duration of the operationand in the mean blood loss in the treatment group. The side-effectsencountered in the treatment group were mild and well acceptedby the women. Oral misoprostol is an effective and safe methodfor cervical dilatation prior to vacuum aspiration in firsttrimester pregnancy.     

Misoprostol for cervical ripening in non-pregnant women: a randomized double-blind controlled trial of oral versus vaginal regimens

BACKGROUND: The objective was to compare the efficacy of oral versus vaginal misoprostol for cervical ripening in non-pregnant women. METHODS: Sixty non-pregnant women scheduled for diagnostic hysteroscopy were randomized by computerized randomization schedule to 400 microg of misoprostol orally (n = 30) or 200 microg vaginally (n = 30) administered 12 h prior to surgery. The diameter of the cervical canal measured with a Hegar dilator, adverse events and any complications were recorded and compared between the two groups. RESULTS: The mean pre- and post-medication cervical canal diameter and cervical diameter difference were 2.00 +/- 1.93 versus 2.37 +/- 1.83 mm (P = 0.453), 5.10 +/- 1.75 versus 5.60 +/- 1.69 mm (P = 0.265) and 3.10 +/- 1.79 versus 3.23 +/- 1.74 mm (P = 0.771) in the oral and vaginal group, respectively. Seven patients in the oral group and one patient in the vaginal group experienced diarrhoea within 24 h of administration of the misoprostol. CONCLUSION: Oral misoprostol 400 microg had similar efficacy in cervical ripening to 200 microg of vaginal misoprostol.     

Mifepristone does not induce cervical softening in non-pregnant women

BACKGROUND: Many techniques have been developed to soften the cervix to reduce complications following surgical dilatation. Progesterone inhibits myometrial contractility and its secretion during pregnancy ensures cervical competence. We used the progesterone antagonist mifepristone as a cervical ripening agent and evaluated its effect prior to office hysteroscopy. METHODS: Fifty-eight healthy non-pregnant women aged 18-50 were studied in a randomized double-blind study. They received mifepristone (200 mg) or placebo 30 h prior to hysteroscopy. A Hegar test was performed prior to drug administration and again before hysteroscopy. A visual analogue pain scale was used to assess pain. RESULTS: Medical history, physical examination and blood tests were similar in both groups, except for serum progesterone which was higher in the study group. Hegar measurement prior to drug ingestion was similar in both groups and after a mean time of 30.3 h increased in both groups. Neither the DeltaHegar measurement nor the pain scale was different in the two groups. There was also no effect of the high progesterone levels. CONCLUSIONS: Unlike its dramatic effect in the pregnant uterus, mifepristone administered 30 h prior to hysteroscopy was not effective in ripening the cervix of non-pregnant women.     

Intracervical sodium nitroprusside versus vaginal misoprostol in first trimester surgical termination of pregnancy: a randomized double-blinded controlled trial

BACKGROUND: Results from small-scale randomized studies on the effectiveness of different preparations of nitric oxide donors in cervical priming before first trimester termination of pregnancies are not consistent. We compared sodium nitroprusside gel to misoprostol, the standard agent for cervical priming in this randomized double-blinded controlled trial. METHODS: Two hundred pregnant patients between 8 to 12 weeks admitted for surgical termination of pregnancy were recruited. They were randomized into either 400 microg vaginal misoprostol and intracervical placebo gel, or 10 mg intracervical sodium nitroprusside gel and placebo tablets 3 h before the procedure. The baseline cervical dilatation and cumulative force required to dilate the cervix from 4 to 9 mm were measured with a tonometer. Blood pressure was measured and side effects were assessed. RESULTS: The cumulative force to dilate the cervix from 4 to 9 mm was significantly higher in the sodium nitroprusside group, and the difference remained when a sub-group analysis was performed according to parity. Baseline cervical dilatation, duration of operation and operative blood loss were all in favour of misoprostol. Transient drop in blood pressure was observed after sodium nitroprusside treatment. CONCLUSIONS: Intracervical sodium nitroprusside is not as effective as misoprostol in cervical priming.     

A randomized study comparing the use of sublingual to vaginal misoprostol for pre-operative cervical priming prior to surgical termination of pregnancy in the first trimester

BACKGROUND: Misoprostol is an effective agent for pre-operative cervical priming before surgical termination of pregnancy in the first trimester. Previous studies have shown that both oral and vaginal routes are equally effective for such a purpose. This study aimed to compare a new route of sublingual administration to the vaginal route of administration for pre-operative cervical priming in first trimester surgical abortion. METHODS: Eighty women with gestational age <12 weeks were randomized by a computer-generated model to receive 400 micro g of misoprostol either sublingually or vaginally 3 h prior to vacuum aspiration. The primary outcome measure was the degree of cervical dilatation, and secondary outcomes included the force required to dilate the cervix from 3 to 8 mm, intra-operative blood loss and incidence of pre-operative side-effects. RESULTS: There was no significant difference in the baseline cervical dilatation (sublingual: 7.6 +/- 1.3 mm; vaginal: 7.7 +/- 0.73 mm), cumulative force required to dilate the cervix from 3 to 8 mm (sublingual: 9.0 +/- 9.8 N; vaginal: 6.6 +/- 5.4 N) and total blood loss (sublingual: 52.1 +/- 20.2 ml; vaginal: 48.3 +/- 12.3 ml). Pre-operative side-effects were also similar. CONCLUSIONS: Both sublingual and vaginal misoprostol are effective in cervical priming before surgical termination of pregnancy in the first trimester. Sublingual misoprostol has the advantage of being more convenient to administer and may be more suitable for day surgery.     

Vaginal misoprostol for cervical ripening before operative hysteroscopy in pre-menopausal women: a double-blind, placebo-controlled trial with three dose regimens

BACKGROUND: To evaluate the effects of vaginal misoprostol on cervical dilatation before operative hysteroscopy in pre-menopausal women. METHODS: Four groups of 12 women were randomly assigned to receive either placebo or vaginal misoprostol in doses of 200, 400 or 800 micro g 4 h before the surgical procedure. The number of patients was calculated with an alpha = 0.01 and beta =0.20 for a difference of 50%. The primary outcome measure was cervical width, assessed by the largest size of Hegar dilator that could be inserted without resistance. The secondary outcomes were subjective assessments of the ease of dilatation and pre-operative pain, as well as adverse effects and complications. RESULTS: There was no difference in the baseline diameter of the cervical opening between the placebo group (6.1 +/- 1.4 cm) and the misoprostol groups (6.3 +/- 2.1 cm). The groups did not differ significantly in the time required for dilatation, ease of dilation, or the number of adverse effects. Pre-operative pain, evaluated by a pain scale, was greater in the treatment groups and was rated at 2.5 +/- 2.3 (P = 0.015), 2.4 +/- 1.2 (P = 0.073) and 2.8 +/- 2.9 (P = 0.012) respectively for each increasing dose group. CONCLUSIONS: Vaginal misoprostol applied 4 h before operative hysteroscopy at three different doses did not reduce the need for cervical dilatation, did not facilitate hysteroscopic surgery, and increased pre-operative pain.     

Does an acidic medium enhance the efficacy of vaginal misoprostol for pre-abortion cervical priming?

Absorption pharmacokinetics reveal a relationship between plasma concentrations of misoprostol and its therapeutic effect. To achieve a constant plasma profile and optimal efficacy, it is important to develop a medium that ensures complete dissolution of vaginal misoprostol tablets. Vaginal misoprostol is said to liquefy better in an acidic medium; thus, the aim of this study was to determine whether a 200 microg misoprostol tablet dissolved in acetic acid would be more efficacious than 200 microg misoprostol dissolved in water for pre-abortion cervical priming. A total of 120 healthy nulliparous women requesting legal termination of pregnancy between 6-12 weeks gestation were allocated randomly to either of the study groups. Vacuum aspiration was performed 3-4 h after insertion of the misoprostol tablet. Using Hegar's dilator, the degree of cervical dilatation before operation was measured. Of 60 women, 14 (23%) achieved a cervical dilatation of >/=8 mm when the misoprostol dose was dissolved in acetic acid; 12 (20%) achieved a similar cervical dilatation when the dose was dissolved in water. The mean cervical dilatation for the acid and water media used was 6.3 mm and 6.2 mm respectively; these differences were not statistically significant, neither were pre-operative and intra-operative blood losses statistically different between the two groups. Twenty-four (40%) and four (7%) respectively of women in whom a water medium was used experienced vaginal bleeding and abdominal pain; 20 (33%) and 0 women respectively among those in whom an acetic acid medium was used experienced vaginal bleeding and abdominal pain. These differences in side effects were not statistically significant. Our study shows that the use of acetic acid to dissolve vaginal misoprostol does not improve the efficacy in achieving successful cervical dilatation for pre-abortion cervical priming.     

Comparison between the sublingual and oral route of misoprostol for pre-abortion cervical priming in first trimester abortions

BACKGROUND: Misoprostol has been used for achieving cervical priming before suction evacuation (SE) by the oral or vaginal route, although both routes have their shortcomings. We evaluated the efficacy of the sublingual versus oral route of misoprostol for cervical priming before SE. METHODS: A prospective clinical trial was carried out in 100 women with a period of gestation of between 6 and 12 weeks who were sequentially allocated to two groups of 50 each. Both groups received 400 microg of misoprostol 3 h prior to SE by either the sublingual or the oral route. RESULTS: Demographically, both groups were similar. For all periods of gestation, sublingual misoprostol significantly improved cervical dilation (P<0.001) with a reduction in duration of surgery (P=0.024) compared with the oral route. Mean (+/- SD) pain scores for the sublingual and oral groups were similar (2.6 +/- 1.4 versus 3.5 +/- 1.1). No major complications occurred in either of the two groups. CONCLUSION: the sublingual route is an effective alternative to oral administration of misoprostol for cervical dilation. To the best of our knowledge, this is the first study to compare the efficacy of the sublingual versus the oral route of misoprostol for cervical priming before SE.     

Effect of local lignocaine gel application for pain relief during suction termination of first-trimester pregnancy: a randomized controlled trial

BACKGROUND: This study evaluated the effectiveness of local lignocaine gel application in pain control during first-trimester suction termination of pregnancy (STOP). METHODS: In this prospective randomized placebo-controlled double-blind trial, 131 women undergoing STOP between 7 and 10 weeks of gestation were studied. They were computer-randomized to receive 2% lignocaine gel or placebo (KY Jelly) locally applied to the cervix 1 min before cervical manipulation/dilatation. They all had cervical priming with misoprostol and premedication with diazepam and pethidine. Pain scores on a verbal analogue scale preoperative, at cervical manipulation/dilatation, intraoperative and 1 h post-operative, as well as the patients' satisfaction level towards pain control, were compared. RESULTS: The lignocaine gel group had significantly reduced overall intraoperative pain score compared with placebo group (P = 0.021). No significant difference in pain score between the two groups was demonstrated at other time points. Subgroup analysis revealed that the difference in overall intraoperative pain scores between the two groups was evident in the multiparous (P = 0.015) but not the nulliparous subjects. CONCLUSION: The use of local lignocaine gel application reduces overall intraoperative pain in multiparous women undergoing first-trimester STOP preceded by misoprostol cervical priming and premedication for conscious sedation.     

Cervical priming with sublingual misoprostol prior to insertion of an intrauterine device in nulliparous women: a randomized controlled trial

BACKGROUND: The copper intrauterine device (IUD) is a highly effective andsafe contraceptive method, also in nulliparous women. However,insertion of an IUD through a narrow cervix may be technicallydifficult. Misoprostol has been shown to be effective for cervicalpriming in non-pregnant women prior to hysteroscopy. METHODS: Eighty nulliparous women requesting an IUD were randomly allocatedto receive sublingually 400 µg misoprostol and 100 mgdiclofenac (misoprostol group) or 100 mg diclofenac alone (controlgroup) 1 h prior to IUD insertion. Cervical dilatation was measuredprior to insertion using Hegar pins. Ease of insertion was judgedby the investigator. Pain, bleeding and side effects were recordedat insertion and until follow-up performed one month later. RESULTS: Following treatment with misoprostol, insertion was significantlyeasier than in the control group [P = 0.039, difference 19.36%,confidence interval (CI) –0.013, 39.99]. Pain estimatedon a visual analogue scale (1–10) showed no evidence ofa difference between the groups. The overall distribution ofside effects did not differ. However, shivering was more commonin the misoprostol group (P = 0.0084, difference 23.27%, CI6.64, 39.90). CONCLUSIONS: Misoprostol facilitates insertion of an IUD, and reduces thenumber of difficult and failed attempts of insertions in womenwith a narrow cervical canal. The optimal regimen of misoprostolremains to be defined.     

Preparation of the cervix for surgical termination of pregnancy in the first trimester

Worldwide, surgical vacuum aspiration is the method of choice of terminating first trimester unwanted pregnancy. Cervical priming prior to surgical evacuation reduces the risks of cervical injury by making the cervix softer and easier to dilate. Over the years, a number of effective methods of cervical priming have became available: osmotic dilators; antiprogesterone and prostaglandins. Of these, prostaglandins remain the most widely used method of cervical preparation. However many of the natural and synthetic analogues of prostaglandins are either expensive or associated with troublesome side-effects. More recently, misoprostol, a synthetic 15-deoxy-16 hydroxy 16-methyl analogue of naturally occurring prostaglandin E, used in the management of peptic ulcers, has established a lead for cervical priming in terms of availability, ease of administration, cost and effectiveness. In fact it appears that both oral and vaginal misoprostol given at dosages of 400 microg are effective for cervical priming when administered 3 h prior to surgical vacuum aspiration. Now that the use of misoprostol for cervical priming has been validated, its widespread use in gynaecological practice is expected.     

Sublingual misoprostol: A better choice for cervical priming before manual vacuum aspiration

Background: Misoprostol is effective for cervical priming before manual vacuum aspiration (MVA). Aim of study was to determine whether sublingual misoprostol with a shorter interval of 2 hours before MVA would be as effective as its standard vaginal administration. Study Design: This randomized control trial included 82 women randomly assigned to receive 400 mcg of misoprostol, either sublingually or vaginally. MVA was performed 2 hours and 3 hours after in sublingual and vaginal group, respectively. Results: Cervical dilatation of 8 mm was achieved within 2 hours in sublingual group. Mean time taken for procedure (14.4 ± 5.3: sublingual group and 16.2 ± 5.7: vaginal group), and blood loss was comparable (12.2 ± 9.7 ml in sublingual group and 13.7 ± 8.5 ml in vaginal group). Conclusion: 2 hour of cervical priming with 400 mcg of sublingual misoprostol before MVA was as good as 3 hours with vaginal administration of the same dose.     

The expression of glutaredoxin is increased in the human cervix in term pregnancy and immediately post-partum, particularly after prostaglandin-induced delivery

Glutaredoxins are glutathione disulphide oxidoreductases catalysing disulphide reductions via a redox active disulphide. We have examined the presence of glutaredoxin in the human cervix, and its differential expression during cervical remodelling in term pregnancy and immediately post-partum as compared to the non-pregnant state. Cervical biopsies were obtained from 24 term-pregnant and 24 post-partal women, of which 10 were taken after spontaneous delivery, 10 after prostaglandin-induced delivery and four after mifepristone-induced delivery, all obtained within 15 min after delivery. Six non-pregnant women served as controls. The tissues were analysed for the glutaredoxin mRNA levels using a solution hybridization method. Glutaredoxin mRNA was expressed in the human cervix, the level increased > or =2-fold at term pregnancy and immediately post-partum. The level of cervical glutaredoxin mRNA from prostaglandin E(2)-treated women was 3-fold higher than after spontaneous ripening and delivery. Localization of glutaredoxin was visualized with immunohistochemistry in cervices from two post-partal women, and was compared to that of thioredoxin. We conclude that glutaredoxin may be involved in the regulation of cervical ripening in humans, particularly in the inflammatory reaction seen during this process. Glutaredoxin mRNA levels are up-regulated after prostaglandin treatment, which is effective and the most commonly used substance for cervical priming and induction of labour.     

Matrix metalloproteinases-2 and -9 and their inhibitors are produced by the human uterine cervix but their secretion is not regulated by nitric oxide donors.

We have investigated the presence of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP) in the human uterine cervix. We postulate that during the process of cervical ripening, there is an increase in the activity of MMP in order to facilitate cervical connective tissue change. We have previously demonstrated that nitric oxide (NO) donors induce cervical ripening in vivo. A secondary hypothesis is that NO donors regulate MMP activity within the human uterine cervix. Cervical tissue biopsies were obtained from both pregnant and non-pregnant subjects. Cervical fibroblasts were cultured from the non-pregnant tissue. MMP-2 was present in conditioned media from pregnant and non-pregnant cervical explants and non-pregnant cervical fibroblasts. MMP-9 secretion was only detected in explants from non-pregnant women. TIMP-1, -2 and -4 were released by all cervical explants and fibroblast preparations. Pregnant women, in the first trimester, were treated with an NO donor (isosorbide mononitrate) in vivo. Cervical explants and fibroblasts from non-pregnant women were treated with the NO donor spermine nonoate in vitro. Treatment with an NO donor either in vivo or in vitro had no effect on the secretion of the MMP or TIMP studied. Further studies evaluating the mechanisms involved in cervical ripening are required.     

Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy

It is known that when misoprostol is given at 200 microg every 3 h after mifepristone pretreatment, the vaginal route is more effective than the oral route. However, women prefer the oral route. This randomized study was to test our hypothesis that oral misoprostol 400 microg is as effective as vaginal misoprostol 200 microg when given every 3 h in termination of second trimester pregnancy after priming with mifepristone. A total of 142 patients was randomly assigned to group 1 (200 mg mifepristone + 400 microg oral misoprostol every 3 h up to five doses) or group 2 (200 mg mifepristone + 200 microg vaginal misoprostol every 3 h up to five doses). The incidence of side-effects and the preference study were assessed through a standardized questionnaire during and after the abortion. For the oral group, both the incidence of diarrhoea (40.0 versus 23.2%, P = 0.03) and the amount of drug used (1734 compared with 812 microg, P < 0.0001) were significantly higher than that of the vaginal group but the incidence of fever appeared to be lower (not significant). There was no significant difference in complete abortion rate: 81.4% in the oral group and 75.4% in the vaginal group. The median induction-abortion interval was similar in the two groups (10.4 versus 10.0 h). The percentage of women who aborted in 24 h was also similar: 57/70 (81.4%) in the oral group and 58/69 (87.0%) in the vaginal group. Overall, 82.0% of women preferred the oral route. Oral misoprostol (400 microg) given every 3 h up to five doses, when combined with mifepristone, was as effective as the vaginal (200 microg) route in second trimester termination of pregnancy. This regimen could also be offered to those women who found repeated vaginal administration unacceptable.     

Vaginal misoprostol as medical treatment for first trimester spontaneous miscarriage.

BACKGROUND: Misoprostol is effective for cervical priming prior to suction evacuation in first trimester pregnancy termination. This is the first randomized study to compare vaginal misoprostol versus expectant treatment in women presenting with spontaneous miscarriage. METHODS: Sixty women presenting with spontaneous miscarriage were recruited to the study at the Queen Mary Hospital between 1998 and 1999. They were randomized to group 1: misoprostol; and group 2: expectant management. Women in the misoprostol group received vaginal misoprostol 400 microg on days 1, 3 and 5. The expectant group was followed up according to the same schedule. Suction evacuation was performed if there was excessive bleeding or abdominal pain; or if a gestational sac was detected by transvaginal scan on day 15. RESULTS: Fifty-nine women completed the trial. Those who did not require suction evacuation up to the time of return of normal menstruation were considered to be successful. The incidence of side-effects was comparable between the two groups. Three women in the expectant group and one in the misoprostol group underwent emergency suction evacuation because of excessive bleeding. The mean duration of vaginal bleeding was similar for both groups (14.6 days in the misoprostol group versus 15.0 days in the expectant group). The successful rate in the misoprostol group was significantly higher than that of the expectant group (83.3 versus 48.3%, P < 0.05). CONCLUSION: We recommend repeated vaginal misoprostol 400 microg given on days 1, 3 and 5 as a treatment option for women with first trimester spontaneous miscarriage.     

Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition

Nitric oxide (NO) has been proposed as a mediator of cervical ripening. We investigated the expression, using Western blotting, and localization, using immunohistochemistry, of the nitric oxide synthase (NOS) enzymes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (bNOS) in the human cervix during pregnancy and parturition. Cervical biopsies were obtained from non-pregnant women, women in the first trimester of pregnancy, and pregnant women at term before and after the onset of labour. Each of the NOS isoforms was localized in the cervices of both non-pregnant and pregnant subjects using immunohistochemistry. iNOS expression was significantly greater in early pregnancy compared with the non-pregnant state (P: < 0.005). iNOS expression was up-regulated further in samples obtained in the third trimester compared with the first trimester. bNOS expression was greater in samples from the first trimester of pregnancy than in non-pregnant samples (P: < 0. 005), but showed no additional increase in late pregnancy or with the onset of labour. eNOS expression was increased in samples obtained in the third trimester both before (P: = 0.002) and after the onset of labour (P: < 0.002) when compared with non-pregnant samples. The increased expression of NOS isoforms in late pregnancy supports the hypothesis that NO is involved in the process of cervical ripening.