Anne Katerine Omland

In vitro fertilization is a successful treatment in endometriosis-associated infertility

OBJECTIVE To assess success rates of IVF and intracytoplasmic sperm injection in women with various stages of endometriosis. DESIGN Retrospective cohort study. SETTING Reproductive medicine unit in a university hospital. PATIENT(S) Infertile women (n = 2,245) with various stages of endometriosis or tubal factor infertility. INTERVENTION(S) IVF or intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S) Dose of FSH, number of oocytes retrieved, fertilization rate, implantation rate, pregnancy rate (PR), live birth/ongoing PR. RESULT(S) Women with endometriosis had similar pregnancy and live birth/ongoing PR as did women with tubal factor infertility, but the American Society for Reproductive Medicine (ASRM) stage I and II endometriosis patients had a lower fertilization rate, and stage III and IV patients required more FSH and had fewer oocytes retrieved. Splitting the stage III and IV groups into patients with and without endometriomas showed that the endometrioma group required more FSH and had a significantly lower pregnancy and live birth/ongoing PR. CONCLUSION(S) With the exception of patients with endometrioma, infertile women with various stages of endometriosis have the same success rates with IVF and intracytoplasmic sperm injection as patients with tubal factor. This contrasts with the systematic review on which the European Society of Human Reproduction and Embryology bases its recommendations.

In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneal endometriosis

Background. To compare the outcome of in vitro fertilization /embryo transfer (IVF‐ET) in unexplained infertility and infertility associated with minimal peritoneal endometriosis.

Risk of breast cancer following fertility treatment – A registry based cohort study of parous women in Norway

Despite increasing numbers of women availing themselves of assisted reproductive technology (ART), effects on cancer risk remain unresolved. Given hormonal exposures, breast cancer risk is of particular concern. The aim of this study is to investigate breast cancer risk amongst women giving birth following ART as compared to that amongst women who gave birth without ART. Data on all women who gave birth in Norway with or without ART, between 1984 and 2010 were obtained from the Medical Birth Registry of Norway (MBRN). 808,834 women eligible for study were linked to the Cancer Registry of Norway. Cox proportional models computed hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer between the two groups, adjusting for age, parity, age at first birth, calendar period and region of residence. In total, 8,037 women were diagnosed with breast cancer during the study period, 138 ART women and 7,899 unexposed. Total follow‐up time was 12,401,121 person‐years (median 16.0); median age at entry was 32.5 years (range18.6–49.9) for ART women and 26.3 (range 10.5–54.6) for unexposed. Women exposed to ART had an elevated risk of breast cancer (adjusted HR 1.20, 95% CI 1.01–1.42). Subgroup analyses gave an HR of 1.30 (95% CI 1.07–1.57) for women treated with IVF and 1.35 (95 % CI 1.07–1.71) for women with follow‐up >10 years, compared with controls. Our findings of increased risk in the study population warrant continued monitoring of women treated with ART as this population advances into more typical cancer age ranges.

Cancer risk among parous women following assisted reproductive technology

STUDY QUESTION Do women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART? SUMMARY ANSWER Without correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses. WHAT IS KNOWN ALREADY Studies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor. STUDY DESIGN, SIZE, DURATION A population-based cohort consisting of all women registered in the Medical Birth Registry of Norway as having given birth between 1 January 1984 and 31 December 2010 was assembled (n = 812 986). Cancers were identified by linkage to the Cancer Registry of Norway. Study subjects were followed from start of first pregnancy during the observational period until the first cancer, death, emigration, or 31 December 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the total study population (n = 806 248), 16 525 gave birth to a child following ART. Cox regression analysis computed hazard ratios (HR) and 95% confidence intervals (CI) comparing cancer risk between ART women and non-ART women; for overall cancer, and for cervical, ovarian, uterine, central nervous system (CNS), colorectal and thyroid cancers, and for malignant melanoma. MAIN RESULTS AND THE ROLE OF CHANCE A total of 22 282 cohort members were diagnosed with cancer, of which 338 were ART women and 21 944 non-ART women. The results showed an elevated risk in one out of seven sites for ART women. The HR for cancer of the CNS was 1.50 (95% CI 1.03– 2.18), and among those specifically subjected to IVF (without ICSI) the HR was 1.83 (95% CI 1.22–2.73). Analysis of risk of overall cancer gave an HR of 1.16 (95% CI 1.04–1.29). Among those who had delivered only one child by the end of follow-up, the HR for ovarian cancer was 2.00 (95% CI 1.08–3.65), and for those nulliparous at entry the HR was 1.80 (95% CI 1.04–3.11). However, all findings became non-significant after correcting for multiple analyses. LIMITATIONS, REASONS FOR CAUTION The results of elevated risk of overall cancer and CNS cancer lost significance when adjusting for multiple analyses, implying an important limitation of the study. The follow-up time was relatively short, especially for ART women. In addition, as the cohort was relatively young, there were few incident cancers, especially for some rarer cancer forms, such as uterine cancer. Risk assessments according to different causes of infertility could not be done. WIDER IMPLICATIONS OF THE FINDINGS In light of the findings in the present study, further studies should be made on risk of CNS and ovarian cancer, and continued monitoring of all those treated with ART is encouraged. Our findings may only be generalizable to women who give birth after ART, and the risk for women who remain nulliparous after ART remains to be assessed. STUDY FUNDING/COMPETING INTEREST The study was funded by the Norwegian National Advisory Unit on Womens Health. All authors claim no competing interests.

Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis-associated infertility after fertilization failure with in vitro fertilization (IVF)

AbstractPurpose: To investigate possible differences between unexplained and stage I endometriosis-associated infertility in ICSI cycles conducted after low fertilization (<20%) in preceding IVF cycles with normal semen parameters. Methods: Retrospective cohort study consisting of patients with unexplained (n=48) and stage I endometriosis-associated infertility (n=43) with a minimum of one IVF cycle with <20% fertilized oocytes and normal semen quality, treated with ICSI from January 1997 to January 2006. Age matched male factor infertility patients (n=91) were used as controls. Results: Diploid fertilization rate was significantly lower in the stage I endometriosis-associated infertility group compared to the unexplained infertility group. Score of the transferred embryos, implantation rate, pregnancy rate and outcome were similar in the two groups. Conclusions: ICSI appears to be an efficient treatment option after fertilization failure with IVF in unexplained and stage I endometriosis-associated infertility.

Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing their first treatment cycle of IVF or ICSI

Objective. To test whether the clinical efficiency of recombinant FSH (rFSH) and highly purified human menotrophin (hMG) differs in terms of pregnancy and live birth rates during the first treatment cycle of IVF or ICSI. Design. Prospective cohort study. Setting. Department of Gynecology and Obstetrics, Rikshospitalet, Oslo University Hospital. Study population. Records of 1,136 infertile couples undergoing their first IVF (n = 682) or ICSI (n = 454) treatments were reviewed. The effect of hMG and rFSH was analyzed for the IVF and ICSI groups separately. Methods. Patients received long term down‐regulation with GnRH agonist and controlled ovarian hyperstimulation with hMG or rFSH. Oocytes were fertilized by IVF or ICSI. Embryos were transferred on Day 2. Main outcome measures. Primary outcome measures were pregnancy and live birth rates, secondary outcome measures were duration of treatment, doses of hMG or rFSH applied, number of oocytes retrieved and the number and quality of embryos obtained. Results. Similar pregnancy and live birth rates were observed with hMG and rFSH. Compared to hMG, treatment cycles with rFSH were characterized by significantly shorter stimulation, lower gonadotrophin consumption, and increased number of oocytes and embryos. Conclusion. We conclude that rFSH and hMG are equivalent in terms of clinical efficacy.

Cancer risk in women treated with fertility drugs according to parity status- A registry-based cohort study

Background: Long-term safety of assisted reproductive techniques (ART) is of interest as their use is increasing. Cancer risk is known to be affected by parity. This study examined the risk of cancer after fertility treatment, stratified by womens parity. Methods: Data were obtained from all women (n = 1,353,724) born in Norway between 1960 and 1996. Drug exposure data (2004–2014) were obtained from the Norwegian Prescription Database (drugs used in ART and clomiphene citrate). The Medical Birth Registry of Norway provided parity status. HRs were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer, and malignant melanoma. Results: In 12,354,392 person-years of follow-up, 20,128 women were diagnosed with cancer. All-site cancer risk was 1.14 [95% confidence interval (95% CI), 1.03–1.26] and 1.10 (95% CI, 0.98–1.23) after clomiphene citrate and ART exposure, respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR, 2.49; 95% CI, 1.30–4.78; and HR, 1.62; 95% CI, 0.78–3.35) versus parous women (HR, 1.37; 95% CI, 0.64–2.96; and HR, 0.87; 95% CI, 0.33–2.27). Elevated risk of endometrial cancers was observed for clomiphene citrate exposure in nulliparous women (HR, 4.49; 95% CI, 2.66–7.60 vs. HR, 1.52; 95% CI, 0.67–3.42). Risk was elevated for breast cancer in parous women exposed to clomiphene citrate (HR, 1.26; 95% CI, 1.03–1.54) for thyroid cancer and among nulliparous women after ART treatment (HR, 2.19; 95% CI, 1.08–4.44). Conclusions: Clomiphene citrate appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity. Impact: Continued monitoring of fertility treatments is warranted. Cancer Epidemiol Biomarkers Prev; 26(6); 953–62. ©2017 AACR.

Infertility treatment and the risk of cancer

BACKGROUND A possible correlation between hormonal stimulation during treatment of infertility and the risk of cancer of the breast, the ovaries, the cervix or the uterus has been investigated in a number of epidemiological studies. The purpose of this article is to review the relevant literature and summarise the findings. KNOWLEDGE BASE: This review article is based on literature searches in the databases MEDLINE, Cochrane and EMBASE. RESULTS No studies showed a specific general correlation between hormonal ovulatory stimulation used as pre-treatment to assisted fertilisation and an increased risk of cancer of the breast, the ovaries, the cervix or the uterus. Most studies detected no increased risk. Some studies, however, showed an increased risk of cancer among certain sub-groups, such as women who have received repeated treatment with clomiphene citrate. INTERPRETATION On the basis of the studies reviewed, the conclusions are ambiguous. It is therefore necessary to monitor the long-term effects of infertility treatment on womens health. Further good-quality large-scale population studies are necessary, with longer follow-up periods and better adjustment for confounding factors.

Literature review on cancer risk in children born after fertility treatment suggests increased risk of haematological cancers.

Medically assisted fertility treatment, including assisted reproductive technology (ART), is increasingly being used and the subsequent child health outcomes are of interest. Some studies have suggested an elevated risk of somatic morbidity, while others have reported an elevated cancer risk. This review summarises the literature on fertility treatments and childhood cancer, based on 23 cohort and case–control studies.