Nan Birgitte Oldereid

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.

Risk of Cancer in Children Conceived by Assisted Reproductive Technology.

BACKGROUND AND OBJECTIVE: An increasing number of children are born after assisted reproductive technology (ART), and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without. METHODS: The Medical Birth Registry of Norway contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway. Follow-up started at date of birth and ended on the date of the first cancer diagnosis, death, emigration, or December 31, 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types. RESULTS: The study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART-conceived children. Risk of overall cancer was not significantly elevated (HR 1.21; 95% CI 0.90–1.63). However, increased risk of leukemia was observed for children conceived by ART compared with those who were not (HR 1.67; 95% CI 1.02–2.73). Elevated risk of Hodgkins lymphoma was also found for ART-conceived children (HR 3.63; 95% CI 1.12–11.72), although this was based on small numbers. CONCLUSIONS: This population-based cohort study found elevated risks of leukemia and Hodgkins lymphoma in children conceived by ART.

Obstetric and neonatal complications in pregnancies conceived after oocyte donation – a systematic review and meta‐analysis

Approximately 50 000 oocyte donation (OD) treatment cycles are now performed annually in Europe and the US.

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.

Pregnancy outcome according to male diagnosis after ICSI with non-ejaculated sperm compared with ejaculated sperm controls.

The aim of this study was to describe pregnancy outcome in couples who had undergone ICSI using non-ejaculated sperm from men with non-obstructive azoospermia, obstructive azoospermia and aspermia compared with the outcome of ICSI with ejaculated sperm from men with severe oligozoospermia, treated during the same time period. This nationwide cohort study included all children born after ICSI with non-ejaculated sperm in Norway, from when the method was first permitted in Norway in April 2004 to the end of 2010, resulting in 420 pregnancies and a total of 359 children. In 235 of these children, the father was diagnosed with obstructive azoospermia, in 72 with non-obstructive azoospermia, in 31 with aspermia, and in 21 the male cause was unclassifiable. The control group consisted of 760 children from 939 pregnancies conceived by ICSI with ejaculated sperm. Sex ratio, birth weight, rate of pregnancy loss and congenital malformations were not significantly associated with sperm origin or the cause of male factor infertility.

The impact of insulin resistance on the outcome of laparoscopic ovarian electrocautery in infertile women with the polycystic ovary syndrome.

In this study we assessed how insulin resistance affects pregnancy rates in infertile women with the polycystic ovary syndrome (PCOS) treated with laparoscopic ovarian electrocautery. Sixty-four PCOS women were included in the study in a consecutive fashion. Following the CIGMA (continuous infusion of glucose with model assessment) test, 28 women were classified as insulin resistant and 36 women as non-insulin resistant. After the ovarian electrocautery patients were observed for 12-18 months. If pregnancy did not ensue, they were referred for one or more cycles of in vitro fertilization (IVF). Following ovarian electrocautery the non-insulin-resistant women more frequently achieved a regular menstrual cycle and ovulation than the insulin-resistant PCOS women. Consequently 18 (50%) of the non-insulin-resistant PCOS women achieved a pregnancy versus only five (18%) of women in the insulin-resistant PCOS group. Following treatment with both ovarian electrocautery and IVF, 27 (75%) of the non-insulin resistant PCOS women achieved a successful pregnancy, while 13 (46%) of the insulin-resistant PCOS group achieved this. In conclusion, insulin resistance may be an important marker of a poor outcome of treatment in PCOS infertility. Further studies are needed to evaluate the possible effect of treatment alternatives to alleviate the unfavorable influences of insulin resistance and hyperinsulinemia on ovulation induction in PCOS women.

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.