Hormonal contraception and pelvic girdle pain during pregnancy: a population study of 91,721 pregnancies in the Norwegian Mother and Child Cohort.

STUDY QUESTION: Is pre-pregnancy hormonal contraception use associated with the development of pelvic girdle pain during pregnancy? SUMMARY ANSWER: In contrast to combined oral contraceptive pills, long lifetime exposure to progestin-only contraceptive pills or the use of a progestin intrauterine device during the final year before pregnancy were associated with pelvic girdle pain. WHAT IS ALREADY KNOWN: Pelvic girdle pain severely affects many women during pregnancy. Smaller studies have suggested that hormonal contraceptive use is involved in the underlying mechanisms, but evidence is inconclusive. STUDY DESIGN, SIZE, DURATION: A population study during the years 1999-2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 91,721 pregnancies included in the Norwegian Mother and Child Cohort Study. Data were obtained by two self-administered questionnaires during pregnancy weeks 17 and 30. MAIN RESULTS AND THE ROLE OF CHANCE: Pelvic girdle pain was present in 12.9% of women who had used combined oral contraceptive pills during the last pre-pregnancy year, 16.4% of women who had used progestin-only contraceptive pills, 16.7% of women who had progestin injections and 20.7% of women who had used progestin intrauterine devices, compared with 15.3% of women who did not report use of hormonal contraceptives. After adjustment for other study factors, the use of a progestin intrauterine device was the only factor based on the preceding year associated with pelvic girdle pain [adjusted odds ratios (OR) 1.20; 95% confidence interval (CI): 1.11-1.31]. Long lifetime exposure to progestin-only contraceptive pills was also associated with pelvic girdle pain (adjusted OR 1.49; 95% CI: 1.01-2.20). LIMITATIONS, REASONS FOR CAUTION: The participation rate was 38.5%. However, a recent study on the potential biases of skewed selection in the Norwegian Mother and Child Cohort Study found the prevalence estimates but not the exposure-outcome associations to be influenced by the selection. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that combined oral contraceptives can be used without fear of developing pelvic girdle pain during pregnancy. However, the influence of progestin intrauterine devices and long-term exposure to progestin-only contraceptive pills requires further study. STUDY FUNDING/COMPETING INTEREST(S): The present study was supported by the Norwegian Research Council. None of the authors has a conflict of interest.

Introducing reproductive life plan-based information in contraceptive counselling: an RCT.

STUDY QUESTION: Can reproductive life plan (RLP)-based information in contraceptive counselling before pregnancy increase women's knowledge of reproduction, and of the importance of folic acid intake in particular? SUMMARY ANSWER: The RLP-based information increased women's knowledge of reproduction including knowledge of folic acid intake. WHAT IS KNOWN ALREADY: Many women have insufficient knowledge of reproduction, including a health-promoting lifestyle prior to conception, and highly educated women in particular postpone childbearing until an age when their fertile capacity has started to decrease. STUDY DESIGN, SIZE, DURATION: The study was an randomized controlled trial with one intervention group (IG) and two control groups (CG1, CG2). A sample size calculation indicated that 82 women per group would be adequate. Recruitment took place during 3 months in 2012 and 299 women were included. The women were randomized in blocks of three. All groups received standard care (contraceptive counselling, Chlamydia testing, cervical screening). In addition, women in the IG were given oral and written RLP-based information about reproduction. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 299 out of 338 (88%) Swedish-speaking women visiting a Student Health Centre were included (mean age 23 years); response rate was 88%. Before the counselling, women in the IG and the CG1 completed a baseline questionnaire, including questions about lifestyle changes in connection to pregnancy planning, family planning intentions and knowledge of reproduction (e.g. the fecundity of an ovum). At follow-up 2 months after inclusion, a structured telephone interview was performed in all groups (n = 262, 88% participation rate). MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference between the groups regarding the mean knowledge score at baseline. The IG scored higher at follow-up than at baseline (P < 0.001); the mean increased from 6.4 to 9.0 out of a maximum 20 points. The women in the CG1 scored no differently at follow-up than at baseline. The difference in the knowledge score between the IG and the two CGs was significant (P < 0.001), whereas no difference was shown between the two CGs. There was no difference between the groups at baseline regarding how many women could mention folic acid intake among the things to do when planning to get pregnant. At follow-up, 22% in the IG, 3% in CG1 and 1% in CG2 mentioned folic acid intake (P < 0.001). At follow-up, more women in the IG also wished to have their last child earlier in life (P < 0.001) than at baseline, while there was no difference in the CG1. LIMITATIONS, REASONS FOR CAUTION: As the study sample consisted of university students, it is possible that the effect of the intervention was connected to a high level of education and conclusions for all women of reproductive age should be drawn with caution. WIDER IMPLICATIONS OF THE FINDINGS: The provision of RLP-based information seems to be a feasible tool for promoting reproductive health. STUDY FUNDING/COMPETING INTEREST(S): Study funding was received from the Faculty of Medicine, Uppsala University, Sweden. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov Identifier NCT01739101.

Tumour incidence in Swedish women who gave birth following IVF treatment.

BACKGROUND: Possible effects on maternal tumour incidence of a full-term pregnancy following IVF treatment with indicated supraphysiologic steroid and peptide hormonal levels in pregnancy remain uncertain. METHODS: National registries were used to compare incidence of non-invasive and invasive tumour disease in Swedish women with live birth following IVF treatment with women with live birth without IVF. RESULTS: The study had a mean follow-up period of 6.2 years in the IVF group and 7.8 years in the non-IVF group, and the mean gestation period (s.d.) for IVF and non-IVF group was 271.0 (21.1) days and 278.5 (14.1) days, respectively. In a multivariate Poisson regression analysis, adjusted rate ratios of 0.70 (0.52-0.92) and 0.93 (0.58-1.43) among IVF women were found for the risk of carcinoma in situ (CIS) of the cervix and breast cancer, respectively. When date of conception plus 1 and 3 years were used as start of follow-up, the rate ratios of CIS of the cervix increased to 0.77 (0.57-1.03) and 0.86 (0.60-1.19), respectively, and the corresponding figures for breast cancer decreased to 0.91 (0.58-1.42) and 0.74 (0.40-1.26). CONCLUSION: Following a relatively short follow-up period, there is little if any increased risk of premenopausal cancer development in women who gave birth after IVF treatment. The women who gave birth after IVF treatment had a decreased incidence of CIS of the cervix and breast cancer, but only the former was statistically significant. However, further studies are necessary to include longer follow-up times.

Does human relaxin-2 affect peripheral blood mononuclear cells to increase inflammatory mediators in pathologic bone loss?

This study was designed to test the hypothesis that relaxin stimulates bone resorption by regulating the production of several mediators that stimulate osteoclast formation. The levels of mediators were measured in response to differing relaxin concentrations in supernatants from peripheral blood mononuclear cells (PBMCs), MCF-7 breast cancer cells, and normal human osteoblasts. Although all cell types expressed mRNA for the relaxin receptor (LGR7), only PBMCs responded to relaxin at physiologic levels by increasing tumor necrosis factor-alpha and interleukin-1beta secretion. The findings indicate that PBMCs should be studied in relation to the effect of relaxin on inflammation and bone destruction caused by osteoclasts.

The effect of various infertility treatments on the risk of preterm birth.

BACKGROUND: The high incidence of preterm birth (<37 weeks gestation) is a major concern in assisted reproductive technology. The objective of this study was to compare the risk of preterm birth from singleton pregnancies following either low technology treatment (intrauterine insemination and donor insemination) or high technology treatment (IVF, ICSI and gamete intra-Fallopian transfer) with that of naturally conceived pregnancies. METHODS: Three cohorts of pregnancies resulting from either low or high technology treatment or from natural conception were included in the study. A number of potential risk factors were adjusted for. RESULTS: The incidence of very preterm birth (<32 weeks of gestation) was not significantly increased in the low technology treatment group (1.0 versus 1.3% in controls) but was significantly higher in the high technology treatment group (5.2%, P < 0.001). In spontaneous, elective Caesarean section (CS) and induced delivery onset, the risk of preterm birth increased gradually from the controls to the low technology treatment group to the high technology treatment group, while for an emergency CS the risk of preterm birth was very high in both treatment groups. CONCLUSIONS: The overall incidence of preterm birth increased significantly from the controls to the low technology treatment group and to the high technology treatment group. Logistic regression analysis showed that younger and older age, previous perinatal death and emergency CS were associated with an increased risk, while a previous live birth reduced the risk. The length of the infertile period did not seem to affect the risk in any of the treatment groups.

Reproductive hormones and blood pressure during pregnancy.

The mechanisms involved in cardiovasular changes during human pregnancy and the complicated aetiology of gestational hypertension are unclear. Reproductive hormones have known effects on the cardiovascular system in the non-pregnant state and in animal systems, but their effects in human pregnancy are uncertain. In this study of pregnant women, the effects of serum concentrations of relaxin, progesterone and oestradiol on arterial blood pressure were studied. Higher serum concentrations of progesterone and relaxin, but not oestradiol, in early pregnancy were related to lower mean systolic blood pressures in the second and third trimesters. No relationship was found between hormonal concentrations and diastolic blood pressures. However, women with a diastolic blood pressure of >90 mmHg in late pregnancy showed statistically significant lower relaxin concentrations in early pregnancy in comparison with women whose diastolic blood pressure was

Reproductive hormones and stress urinary incontinence in pregnancy.

BACKGROUND: The cause of transient stress urinary incontinence during pregnancy remains uncertain. Anatomical change, such as a pressure effect of the enlarged uterus, changes in renal function, and alterations in bladder and urethral function have been proposed. There is little information about the role of reproductive hormones in stress urinary incontinence with onset during pregnancy. METHODS: In a prospective, longitudinal, observational cohort study 200 consecutive women attending in early pregnancy were observed by repeated measurements of stress urinary incontinence, its possible determinants as well as serum concentrations of progesterone, estradiol and relaxin. RESULTS: The prevalence rate of stress urinary incontinence increased to a stable level of about 25% from mid-pregnancy and increased with parity. A higher serum relaxin value early in pregnancy was correlated to a lower prevalence rate of stress urinary incontinence with onset during pregnancy, also when the influence of potentially important factors was taken into account in a multivariate analysis. No significant difference was shown regarding serum concentrations of estrogen or progesterone, maternal age, weight gain, time since last delivery or smoking, although this can be due to a small sample size. CONCLUSION: The reproductive hormone relaxin might have a role in maintaining urinary continence during pregnancy. A mechanism is uncertain.

Reproductive hormones and aminoterminal propeptide of type III procollagen in serum as early markers of pelvic pain during late pregnancy.

OBJECTIVE: The object was to study serum concentrations of reproductive hormones and aminoterminal propeptide of type III procollagen in early pregnancy as markers of pelvic pain (sacral pain or symphyseal pain) during later pregnancy. STUDY DESIGN: A prospective, clinical cohort study was performed, with repeated examinations of 200 women. RESULTS: Serum concentrations of relaxin and serum concentrations of propeptide of type III procollagen (a collagen turnover marker) measured in early pregnancy were significantly correlated with pelvic pain with onset during pregnancy and reported in late pregnancy (positively and negatively, respectively). In a multivariate analysis, relaxin and propeptide of type III procollagen concentrations remained independently and significantly correlated with pelvic pain. CONCLUSION: Serum concentrations of relaxin and propeptide of type III procollagen measured in early pregnancy may reflect the cause of and indicate an increased risk of pelvic pain (back pain or symphyseal pain) during late pregnancy. The mechanism is unclear.

Back pain in in-vitro fertilized and spontaneous pregnancies.

The influence of ovarian stimulation in in-vitro fertilization (IVF) on the prevalence of back pain with onset during pregnancy was studied in 31 women who became pregnant after IVF treatment and compared with that of 200 spontaneously pregnant women. A two times higher prevalence rate of sacral pain in late pregnancy was reported among IVF pregnant women (P < 0.0001), as well as a significantly higher prevalence rate of positive results of pelvic pain provocation tests performed in late pregnancy (0.0001 < or = P < or = 0.015), as compared with that of the spontaneously pregnant women. Among the IVF pregnant women, there was a significant positive correlation between relaxin concentrations in early pregnancy and the outcome of pelvic pain provocation tests (0.44 < or = r < or = 0.51, P < 0.05). In addition, the serum relaxin concentration was the factor that best explained differences in sacral pain prevalence. When the influence of serum relaxin concentration on back pain prevalence was taken into account, women carrying multiple pregnancies had no more pain than women carrying singletons, and IVF pregnant women had no more pain than spontaneously pregnant women. These results support the hypothesis that relaxin is involved in the generation of pelvic pain in pregnant women.

Serum relaxin, symphyseal pain, and back pain during pregnancy.

OBJECTIVE: Our purpose was to study the relationship between serum relaxin levels and back pain during pregnancy. STUDY DESIGN: A prospective clinical cohort study with repeated examinations was performed. RESULTS: There was an initial increase of relaxin levels until a peak value at the twelfth week followed by a decline until the seventeenth week. Thereafter stable serum levels around 50% of the peak value were recorded. Three months after delivery serum relaxin was not detectable. There was a significant correlation between mean serum relaxin levels during the pregnancy and symphyseal pain or low back pain occurring during late pregnancy as measured by medical history or pain-provoking test. CONCLUSION: Relaxin is known to remodel pelvic connective tissue in several mammalian species during pregnancy. The current data suggest that relaxin might be involved in the development of pelvic pain in pregnant women.

Discriminatory power of tests applied in back pain during pregnancy.

STUDY DESIGN: A longitudinal, prospective, observational cohort study. OBJECTIVES: To assess the relationship between clinical back status and reported pain locations during and after pregnancy. SUMMARY OF BACKGROUND DATA: Back pain during pregnancy is a frequent clinical occurrence, even during the early stages of pregnancy. The cause is unclear. There are few data describing the results of a general physical examination of the back during pregnancy and there are no data on serial examinations. Such data could provide information about what structures cause the pain, which might have implications for the choice of treatment. METHODS: A cohort of 200 consecutive women attending an antenatal clinic was observed throughout the pregnancy terms, and repeated measurements of back pain and its possible determinants were taken using questionnaires and physical examinations in a standardized way, including a series of tests of configuration, mobility, and pain provocation. RESULTS: Pain provocation tests were better at discriminating among women who reported back pain from women who reported no back pain from tests of configuration or mobility. The discriminatory power of the tests was better in the lower part of the spine than in the upper part. The best discrimination was achieved by combining some of the tests. CONCLUSIONS: The results indicate that not one but several pain-releasing structures may be involved. These are probably the various pelvic ligaments, which may form a functional unit. These findings may have therapeutic implications.

Supraphysiological serum relaxin concentration during pregnancy achieved by in-vitro fertilization is strongly correlated to the number of growing follicles in the treatment cycle.

In order to analyse the relationship between the ovarian response to stimulation in in-vitro fertilization (IVF) treatment cycles and relaxin concentrations during subsequent pregnancies, 31 healthy women pregnant after IVF treatment were studied prospectively. The maximum number of follicles observed from day -4 to day -2 in relation to ovum retrieval and the number of oocytes recovered were recorded. In addition, blood samples were drawn in the follicular phase, the luteal phase, early pregnancy and at gestational weeks 12, 16, 20, 27 and 35 to assess oestradiol, progesterone, human chorionic gonadotrophin and relaxin. The maximum numbers (mean +/- SEM) of follicles observed and oocytes recovered were 9.0 +/- 0.6 and 6.1 +/- 0.5 respectively. The supraphysiological mean relaxin values were strongly correlated to the maximum number of follicles observed (r = 0.72, P < 0.0001) and the number of oocytes recovered (r = 0.64, P < 0.0001), indicating that the source of increased relaxin production during IVF pregnancy might be the ovary. These results are supported by experimental data. In the present study, the occurrence of multiple pregnancy was not associated with higher relaxin concentrations, which is further support for the hypothesis that the ovary is the main source of serum relaxin.

Back pain during pregnancy: a prospective study.

STUDY DESIGN: A longitudinal, prospective, observational, cohort study. OBJECTIVES: To describe the natural history of back pain occurring during pregnancy and immediately after delivery. SUMMARY OF BACKGROUND DATA: Back pain during pregnancy is a frequent clinical problem even during the early stages of pregnancy. The cause is unclear. METHODS: A cohort of 200 consecutive women attending an antenatal clinic were followed throughout pregnancy with repeated measurements of back pain and possible determinants by questionnaires and physical examinations. RESULTS: Seventy-six percent reported back pain at some time during pregnancy. Sixty-one percent reported onset during the present pregnancy. In this group, the prevalence rate increased to 48% until the 24th week and then remained stable and declined to 9.4% after delivery. The reported pain intensity increased by pain duration. The pain score correlated closely to self-rated disability and days of sickness benefit. CONCLUSIONS: Back pain during pregnancy is a common complaint. The 30% with the highest pain score reported great difficulties with normal activities. The back pain started early in pregnancy and increased over time. Young women had more pain than older women. Back pain starting during pregnancy may be a special entity and may have another origin than back pain not related to pregnancy.

Serum levels of relaxin during the menstrual cycle and oral contraceptive use.

Serum relaxin levels were analysed in 12 healthy women every other day during the menstrual cycle and during a second cycle on oral contraceptives. Relaxin levels in 7 women with posterior pelvic and lumbar pain were also measured. Relaxin was detected during both the follicular and luteal phases of the menstrual cycle in some of the healthy women. Serum levels were further increased during the use of oral contraceptives. Oestradiol levels in the untreated women correlated to the relaxin levels. Women with posterior pelvic and lumbar pain had higher relaxin levels than did healthy women, a finding that needs to be further explored. Our data indicate the existence of sources for relaxin production other than the corpus luteum in the non-pregnant woman. Endogenous and exogenous oestrogens may stimulate the production of relaxin.

PIP: In Sweden, clinicians took blood samples every other day during one menstrual cycle from 12 healthy women aged 19-42 taking no medication and during a second menstrual cycle from 9 of these women while using a combined oral contraceptive (OC) (150 mcg desogestrel + 30 mcg ethinyl estradiol). They also took samples from a second group of 7 women, 26-42 years old, with a long history of posterior pelvic pains and symptoms in the lower lumbar region during 2 consecutive menstrual cycles. The 7 women did not use OCs but did take paracetamol. The researchers aimed to measure the serum relaxin levels in all the women to determine whether OCs inhibit relaxin secretion and to determine whether changes in relaxin secretion causes posterior pelvic pain. 7 of the 12 healthy women had detectable levels of relaxin during either the follicular or luteal phases or both phases of the menstrual cycle. Relaxin secreted during both phases suggests that the corpus luteum is not the only source of relaxin in nonpregnant women, as commonly believed. As estradiol levels increased so did the relaxin levels (r = 0.44; p 0.05). During OC use, 6 of the 9 women had detectable levels of relaxin. The mean relaxin levels were higher during OC use than during the non-OC cycle (range, 20-255 vs. 20-135 ng/l), except during days 26-32. In fact, the number of relaxin measurements above the detection limit (20 ng/l) during OC use (i.e., anovulation) was much higher than during the normal ovulatory cycle (40 vs. 20; p 0.001). It appears that relaxin secretion does not depend on ovulation. The positive correlation between estradiol and relaxin levels and the increased relaxin levels during OC use suggests that estradiol and ethinyl estradiol regulate relaxin synthesis. All 7 women with posterior pelvic pain had detectable serum relaxin levels. They had detectable relaxin levels significantly more often than did healthy women (p 0.001). Further research is needed to understand the pathophysiological role of relaxin in lower back pain.