Nitrofurantoin in pregnancy

Urinary tract infection is common in pregnancy and a frequent reason for with antibiotic treatment. Nitrofurantoin has been used for many years and is generally thought to be safe in pregnancy; however, there have been some reported associations with malformations, including enophthalmia and cleft palate.

Goldberg et al. report a large-scale retrospective cohort study examining pregnancy outcomes in women exposed to nitrofurantoin in the first trimester. The authors analysed 105 000 pregnancies in an Israeli hospital between 1999 and 2009, including 1112 terminations for medical reasons. Of these, 1329 women had been exposed to nitrofurantoin in the first trimester of their pregnancy. Data on malformations were gathered from ultrasound of fetuses aborted for malformations, from newborn examinations and from infant hospitalisations up to 12 months of age. The rate of major malformations was 5.7 per cent in the nitrofurantoin group and 6.2 per cent in the non-exposed group. There was no increased risk after adjustment for maternal age, parity, ethnic group, pre-gestational diabetes, medical pregnancy termination and smoking during pregnancy. The authors concluded that nitrofurantoin does not increase fetal malformation if used in the first trimester.

Goldberg, O, Koren, G, et al. Exposure to nitrofurantoin during the first trimester of pregnancy and the risk for major malformations. Journal of Clinical Pharmacology, 2013, 53, published online.

IUDs and dysmenorrhea

Intrauterine devices (IUDs) containing either copper or levonorgestrel
(Mirena) are widely used throughout the world. This Swedish longitudinal population-based study reports on the association between IUDs and dysmenorrhoea. The study is based in Gothenburg and, in 1981, randomly selected one in four of all 19-year-old women living in the city to receive a questionnaire regarding contraception, reproductive history, menstrual symptoms and other health data. They then received similar questionnaires every five years. Similar recruiting was performed in 1991 and 2001, except that one-in-three sampling was used. Women recruited in 1991 and 2001 also received questionnaires at five-year intervals. The authors report in 1981 91 per cent of invited women agreed to participate in the study, with rates of 82 per cent and 77 per cent in 1991 and 2001. In 2006, 54 per cent of the women recruited in 1982 were still participating, 25 years after their initial contact.

The study reported that IUD use in their population ranged from 16 per cent of women at 29 years old to 39 per cent at 44 years old. Copper-containing IUDs were more common in the younger women while levonorgestrel IUDs were more common in the older women. As far as dysmenorrhoea symptoms were concerned, women reported a significant reduction in dysmenorrhoea as they became older or had children. They did not report a significant change in dysmenorrhoea when using the copper-containing IUD compared to other contraceptives. They did, however, find both the levonorgestrel IUD and the combined oral contraceptive pill were associated with a reduction in dysmenorrhoea when compared to other contraceptive methods.

Lindh, I and Milsom, I. The influence of intrauterine contraception on the prevalence and severity of dysmenorrhoea: a longitudinal population study. Human Reproduction 2013, 28: 1953-1960.

Long-term outcomes of endometrial ablation

Endometrial ablation is the permanent destruction of the endometrium intended to reduce menstrual bleeding. First-generation techniques included rollerball ablation and laser ablation under direct hysteroscopic vision. Second-generation techniques are now more common and include thermal balloon (for example, Thermachoice, Cavaterm, Thermablate), microwave (Microsulis) and bipolar radiofrequency ablation (for example, Novasure). In many cases, endometrial ablation is attractive to women seeking to reduce menstrual flow while avoiding the side effects of medication or hysterectomy.

This meta-analysis focused on recent (since 2010) randomised controlled trials (RCTs) or cohort studies examining the outcome of second-generation endometrial ablation, at 12 months or more post-procedure. Daniels identified 13 studies, including four RCTs. Results indicated a higher rate of amenorrhea in the bipolar radiofrequency ablation (ranged from 55–97 per cent amenorrhea from 4.5 to eight years post-procedure in different studies) compared to thermal balloon techniques (range from 13–58 per cent amenorrhea from two to five years post-procedure). Rates of patient satisfaction were only reported for thermal balloon and radiofrequency ablation techniques, but were generally high, ranging from 60–93 per cent. The author also reported that around 20–25 per cent of women undergoing endometrial ablation have a second procedure, either a repeat ablation or a hysterectomy. She reported that 6–11 per cent of women having a radiofrequency ablation after five years had repeat intervention, while the comparable rates are 19–25 per cent for thermal balloon ablation.

Endometrial ablation is not intended as a sterilisation technique, with women recommended to use contraception. However, pregnancies are reported and as this study reports they are associated with poor obstetric outcomes. One study identified 123 pregnancies following endometrial ablation. Nearly half were terminated on maternal request while of the 64 that continued 28 per cent miscarried, 16 per cent had preterm rupture of membranes and 31 per cent delivered prematurely. Placental adherence was a complication in 17 of the 64 pregnancies and ten pregnancies resulted in hysterectomy.

In summary, endometrial ablation is an effective treatment for heavy menstrual bleeding for many women. The current review showed an increased rate of amenorrhea for the radiofrequency ablation technique compared to the thermal balloon technique, with both techniques having high rates of patient satisfaction. It is very important that women are aware of the need for contraception following endometrial ablation, given the poor pregnancy outcomes in women who do become pregnant following ablation.

Daniels, JP. The long-term outcomes of endometrial ablation in the treatment of heavy menstrual bleeding. Current Opinion in Obstetrics and Gynecology 2013, 25: 320-326.