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  • 1.
    Brand, J. S.
    et al.
    Utrecht, The Netherlands.
    Onland-Moret, N. C.
    Utrecht, The Netherlands.
    Eijkemans, M. J. C.
    Utrecht, The Netherlands.
    Tjönneland, A.
    Copenhagen, Denmark .
    Roswall, N.
    Copenhagen, Denmark .
    Overvad, K.
    Aarhus, Denmark .
    Fagherazzi, G.
    Villejuif, France.
    Clavel-Chapelon, F.
    Villejuif, France.
    Dossus, L.
    Villejuif, France.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. Heidelberg, Germany .
    Grote, V.
    Heidelberg, Germany .
    Bergmann, M. M.
    Potsdam, Germany.
    Boeing, H.
    Potsdam, Germany.
    Trichopoulou, A.
    Athens, Greece.
    Tzivoglou, M.
    Athens, Greece.
    Trichopoulos, D.
    Athens, Greece; Boston, MA 02115, USA.
    Grioni, S.
    Milan, Italy.
    Mattiello, A.
    Naples, Italy.
    Masala, G.
    Florence, Italy.
    Tumino, R.
    Ragusa, Italy.
    Vineis, P.
    Torino, Italy; London, UK.
    Bueno-De-Mesquita, H. B.
    The Netherlands; London, United Kingdom; Kuala Lumpur, Malaysia .
    Weiderpass, E.
    Norway; Stockholm, Sweden; Helsinki, Finland .
    Redondo, M. L.
    Asturias, Spain.
    Sanchez, M. J.
    Spain.
    Huerta Castano, J. M.
    Spain.
    Arriola, L.
    San Sebastian, Spain.
    Ardanaz, E.
    Spain.
    Duell, E. J.
    Barcelona, Spain.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Franks, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Malmö, Sweden.
    Butt, S.
    Malmö, Sweden.
    Nilsson, P.
    Malmö, Sweden.
    Khaw, K. T.
    Cambridge, UK.
    Wareham, N.
    Cambridge, UK.
    Travis, R.
    Oxford, UK.
    Romieu, I.
    Lyon, France.
    Gunter, M. J.
    London, UK .
    Riboli, E.
    London, UK .
    van der Schouw, Y. T.
    Utrecht, The Netherlands.
    Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition2015In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, no 6, p. 1491-1498Article in journal (Refereed)
    Abstract [en]

    STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.

  • 2. Crawshaw, Marilyn
    et al.
    Adams, Damian
    Allan, Sonia
    Blyth, Eric
    Bourne, Kate
    Bruegge, Claudia
    Chien, Anne
    Clissa, Antonia
    Daniels, Ken
    Glazer, Ellen
    Haase, Jean
    Hammarberg, Karin
    Van Hooff, Hans
    Hunt, Jennie
    Indekeu, Astrid
    Johnson, Louise
    Kim, Young
    Kirkman, Maggie
    Kramer, Wendy
    Lalos, Ann
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lister, Charles
    Lowinger, Phyllis
    Mindes, Erica
    Monach, Jim
    Montuschi, Olivia
    Pike, Sheila
    Powell, Victoria
    Rodino, Iolanda
    Ruby, Alice
    Schrijvers, Anne Margriet
    Semba, Yukari
    Shidlo, Ruth
    Thorn, Petra
    Tonkin, Lois
    Visser, Marja
    Woodward, Julia
    Wischmann, Tewes
    Yee, Samantha
    Zweifel, Julianne E.
    Disclosure and donor-conceived children2017In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 32, no 7, p. 1535-1536Article in journal (Refereed)
  • 3. Hultling, C
    et al.
    Rosenlund, B
    Richard, Levi
    Fridström, M
    Sjöblom, P
    Hillensjö, T
    Assisted ejaculation and in-vitro fertilization in the treatment of infertile spinal cord-injured men: the role of intracytoplasmic sperm injection.1997In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, no 3, p. 499-502Article in journal (Refereed)
    Abstract [en]

    The objective of the present longitudinal descriptive study was to extend previous observations on the benefit of in-vitro fertilization (IVF) in cases of anejaculatory infertility due to spinal cord injuries (SCI) and to report results achieved by intracytoplasmic sperm injection (ICSI). The study was performed in a national referral unit for SCI, Spinalis SCI Research Unit, the Karolinska Institute. The patient material consisted of couples with SCI men seeking treatment for their infertility. The inclusion criteria were: stable relationship, motile spermatozoa in a diagnostic sample and no female contraindications. Spermatozoa were retrieved through electroejaculation or vibratory stimulation. If the sperm quality was judged to be sufficient, standard IVF was performed. ICSI was employed if the semen quality was extremely poor. We have treated 25 couples in 52 cycles, leading to 81 ovum retrievals and 47 embryo transfers. Total sperm counts were very variable (0.01-978 x 10(6)). Before the introduction of ICSI the fertilization rate was 30%. ICSI increased the fertilization rate to 88%. There was no association between the pregnancy rate and the sperm count, level of injury or fertilization technique. A total of 16 clinical pregnancies was established, leading to 11 deliveries. This gives a cumulative pregnancy rate per couple of 56%.

  • 4.
    Idahl, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kumlin, Urban
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olofsson, Jan I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Demonstration of Chlamydia trachomatis IgG antibodies in the male partner of the infertile couple is correlated with a reduced likelihood of achieving pregnancy2004In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 19, no 5, p. 1121-1126Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The objective of this study was to determine the prevalence of Chlamydia trachomatis among both men and women seeking help at an infertility clinic, and to prospectively follow the effect of previous infection on pregnancy rates and pregnancy outcome after a long follow-up period (mean 37 months). 

    METHODS: A total of 244 infertile couples was tested for C. trachomatis IgG antibodies, and IgG(+) couples were also tested for C. trachomatis DNA by PCR in a first-void urine sample. Study parameters were serology, PCR results, clinical diagnoses, treatments, pregnancy rates and pregnancy outcome. As controls, age-matched and spontaneously pregnant women were also tested with serology. 

    RESULTS: The prevalence of IgG antibodies was 24.2, 20.1 and 15.6% among infertile women, infertile men and control women respectively. The prevalence of C. trachomatis DNA was 6.8 and 7.1% among tested women and men respectively. The presence of C. trachomatis IgG antibodies in women was related to tubal factor infertility (TFI) (P = 0.002). Decreased pregnancy rates were seen in couples where the man was IgG(+) (P = 0.005) with no relationship to TFI. Among women who achieved pregnancy, there was no difference in pregnancy outcome between IgG(+) or negative couples. 

    CONCLUSIONS: C. trachomatis IgG antibodies in the man of the infertile couple was related to decreased pregnancy rates and to the presence of IgG antibodies in the woman. There was a high prevalence of asymptomatic persistent infections among infertile couples.

  • 5.
    Kero, Anneli
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lalos, Ann
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Increased contraceptive use one year post-abortion2005In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 20, no 11, p. 3085-3090Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the study was to investigate the impact of abortion on contraceptive use, partner relationship and sexual satisfaction. METHODS: In a longitudinal study, 58 women answered a pre-abortion questionnaire and participated in two interviews, one in connection with the abortion and a second 1 year later. RESULTS: Most women (40/58) had retained the same partner 1 year after the abortion. More than half of these (22/40) experienced no change in the quality of the partner relationship, while the rest (18/40) had deepened their relationship. Furthermore, the majority of the women (45/58) had not experienced any negative influence on their sexual satisfaction. Most women who were sexually active 1 year post-abortion (42/47) used some contraceptive method; the number who used hormonal methods or intrauterine devices had, for example, increased from four to 35, although one-third of them had been doubtful about these methods before abortion. Conversely, 15 women had tried these methods during the follow-up year but had not continued because of negative effects. Overall, contraceptive use 1 year post-abortion had increased. CONCLUSIONS: To achieve well-founded decisions about contraceptives, counsellors should be aware of women’s ambivalence about the use of modern, effective contraceptive methods. In order to prevent abortion it is important to discuss gender differences in sexual behaviour and encourage communication with both sexes about the pros and cons of coitus-dependent and coitus-independent methods.

  • 6.
    Kero, Anneli
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lalos, Ann
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Högberg, Ulf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Jacobsson, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    The male partner involved in legal abortion1999In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 14, no 10, p. 2669-2675Article in journal (Refereed)
    Abstract [en]

    This study comprises 75 men who have been involved in legal abortion. The men answered a questionnaire concerning living conditions and attitudes about pregnancy and abortion. Most men were found to be in stable relationships with good finances. More than half clearly stated that they wanted the woman to have an abortion while 20 stressed that they submitted themselves to their partner's decision. Only one man wanted the woman to complete the pregnancy. Apart from wanting children within functioning family units, the motivation for abortion revealed that the desire to have children depended on the ability to provide qualitatively good parenting. More than half the men had discussed with their partner what to do in event of pregnancy and half had decided to have an abortion if a pregnancy occurred. More than half expressed ambivalent feelings about the coming abortion, using words such as anxiety, responsibility, guilt, relief and grief. In spite of these contradictory feelings, prevailing expectations concerning lifestyle make abortion an acceptable form of birth control. A deeper understanding of the complexity of legal abortion makes it necessary to accept the role of paradox, which the ambivalence reflects. Obviously, men must constitute a target group in efforts to prevent abortions.

  • 7. Kristiansson, P
    et al.
    Björ, O
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Wramsby, H
    Tumour incidence in Swedish women who gave birth following IVF treatment.2007In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 22, no 2, p. 421-6Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Lalos, A
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Breaking bad news concerning fertility.1999In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 14, no 3, p. 581-5Article in journal (Refereed)
  • 9.
    Lalos, Ann
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Daniels, K
    Gottlieb, C
    Lalos, Othon
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Recruitment and motivation of semen providers in Sweden2003In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 18, no 1, p. 212-216Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Legislation in Sweden requires that semen providers are prepared to be identified to offspring (at maturity) should this be requested. This study presents views of semen providers in Sweden regarding factors associated with their recruitment and motivation. METHODS: All semen providers (n = 30) in two clinics in different parts of Sweden participated in a questionnaire survey and both quantitative and qualitative data are reported. RESULTS: While there were some important demographic differences between the two clinic populations, there was total agreement that the desire to assist infertile couples was the sole or main motivating factor in becoming a semen provider. Monetary reward was not reported by respondents to be an important motivator, although at least 50% of the providers in both clinics thought that payment should be made and reimbursement of expenses was reported as being important. Men responded to both advertising and personal experiences or contacts they had with infertile couples. The involvement and support of the semen provider’s partner was regarded as important. CONCLUSIONS: Semen providers can be recruited within a system that requires them to be prepared to be identified to offspring in the future. The characteristics of such providers vary, but are typified by a strong desire to assist infertile couples.

  • 10.
    Lalos, Ann
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Gottlieb, Claes
    Lalos, Othon
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Legislated right for donor-insemination children to know their genetic origin: a study of parental thinking.2007In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 22, no 6, p. 1759-1768Article in journal (Refereed)
  • 11. Lindholm, Åsa
    et al.
    Blomquist, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Dahlbom, Ingrid
    Hansson, Tony
    Sundström Poromaa, Inger
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls.2011In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 26, no 6, p. 1478-85Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: BACKGROUND; Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue.

    METHODS: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR.

    RESULTS: Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-α (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost.

    CONCLUSIONS: Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.

  • 12. Liu, Y X
    et al.
    Peng, X R
    Chen, Y J
    Carrico, W
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Prolactin delays gonadotrophin-induced ovulation and down-regulates expression of plasminogen-activator system in ovary.1997In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, no 12, p. 2748-55Article in journal (Refereed)
    Abstract [en]

    This study was conducted to determine whether prolactin (PRL) suppresses gonadotrophin-induced ovulation and disturbs the co-ordinated gene expression of tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) in rat ovary. Immature female rats were injected with 10 IU pregnant mare's serum gonadotrophin to stimulate follicle growth, and 48 h received different doses of prolactin followed by 7 IU human chorionic gonadotrophin (HCG). The oviducts were examined for the presence of ova, and the amounts of tPA and PAI-1 mRNA present in the ovary were measured at various times after the hormone treatment. PRL had no significant effect on ovarian weight but caused a dose-dependent decrease in ovulation number. In the control animals receiving HCG alone, 13.3 +/- 1.3 (mean +/- SEM) ova/oviduct were found; while in animals receiving HCG plus 50, 100 or 200 microg PRL, the ovulation number was dose-dependently suppressed by 53.6, 66.9 and 76% respectively at 18 h after treatment. PRL suppression of HCG-induced ovulation was time-dependent. By 24 h after treatment, the number of ova in the oviducts in HCG- and HCG plus PRL-treated groups was not significantly different. PRL also suppressed HCG-induced tPA gene expression in a dose- and time-dependent manner. At all time points examined, tPA mRNA content of whole ovaries and granulosa cells (GC) in PRL-treated groups was lower than in the HCG-treated controls. The activities of PAI-1 in ovarian extracellular fluid (OEF) and PAI-1 mRNA in the theca-interstitial cells (TI) in the PRL-treated groups were higher than in the HCG-treated controls. The highest stimulation by PRL of PAI-1 activity in OEF and of PAI-1 mRNA in TI was observed at 9 h and 6 h after HCG treatment respectively. The localization of tPA and PAI-1 antigens in the ovaries was consistent with changes in the mRNA and activity levels. These data suggest that PRL temporarily delays, but does not completely inhibit, HCG-induced ovulation, which may be caused by a suppression of PA-mediated proteolysis.

  • 13.
    Ottander, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nakata, M
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Liu, K
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, J I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Compartmentalization of human chorionic gonadotrophin sensitivity and luteinizing hormone receptor mRNA in different subtypes of the human corpus luteum1997In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, no 5, p. 1037-1042Article in journal (Refereed)
    Abstract [en]

    The relationship was investigated between different ultrasonographically defined subtypes of the human corpus luteum and progesterone production. Twenty-one women in the mid-luteal phase who underwent laparotomy for benign uterine conditions volunteered for this study. The corpus luteum was identified by preoperative ultrasound and classified into four types according to earlier established criteria, where types a and c were centrally hypoechoic, types b and d were centrally echogenic, types a and b had thin surrounding 'walls' (<3 mm) and types c and d had thick walls (<3 mm). After luteectomy, the theca externa capsule was removed and tissue from directly beneath the surface ('peripheral region') and the layer immediately beneath ('inner region') minced into 4-6 mg pieces. Following preincubation, pieces were incubated for 3 h at 37 degrees C in HEPES-minimal essential medium buffer with or without human chorionic gonadotrophin (HCG; 10 IU/ml), and subsequently progesterone accumulation in the medium was determined by radioimmunoassay. The highest progesterone production was consistently seen in the peripheral region. Type a had a significantly (P > 0.01) lower progesterone production (3.2 +/- 1.5 nmol/g tissue wet weight, mean +/- SEM, n = 4) than that of types b, c and d (17.7 +/- 3.5 nmol/g tissue wet weight, n = 9). All types responded to HCG with an almost two-fold increase in progesterone production. However, the maximal progesterone produced following stimulation by HCG in the type a corpus luteum was <50% of the basal (unstimulated) progesterone synthesis of any other type of corpus luteum. Using in-situ hybridization, with a primate RNA probe complementary to the region coding the extracellular part of the luteinizing hormone (LH) receptor, a highly localized expression of LH receptor mRNA to the peripheral region was found. Negligible or low levels of expression were found in the theca externa capsule and the inner region. No obvious correlations between the different subtypes of corpora lutea and LH receptor mRNA expression were seen. Thus, the ultrasonographic detection of a thin-walled and centrally hypoechoic corpus luteum correlates well with reduced progesterone secretion. The underlying cellular mechanism does not appear to involve a diminished sensitivity to the gonadotrophic stimulation by LH or HCG.

  • 14. Persson, S.
    et al.
    Elenis, E.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Department of Obstetrics and Gynecology, Sundsvall County Hospital, Sundsvall 85186, Sweden.
    Kramer, M. S.
    Yong, E-L
    Sundström-Poromaa, I
    Fecundity among women with polycystic ovary syndrome (PCOS)-a population-based study2019In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 34, no 10, p. 2052-2060Article in journal (Refereed)
    Abstract [en]

    STUDY QUESTION: Does the long-term fecundity of women with polycystic ovary syndrome (PCOS) differ from those without PCOS?

    SUMMARY ANSWER: Cumulative probability of childbirth is similar between women with and without PCOS.

    WHAT IS KNOWN ALREADY: PCOS is the main cause of anovulatory infertility in women after menarche. Previous studies indirectly suggest that fecundity in women with PCOS over the longer term may not be lower than in women without PCOS.

    STUDY DESIGN, SIZE, DURATION: This is a population-based study using four linked Swedish national registries. A total of 45 395 women with PCOS and 217 049 non-PCOS women were included. Follow-up began at the age of 18 years and continued for a maximum of 26 years, from 1989 to the end of 2015. Childbirth was the main outcome, as identified from the Medical Birth Register.

    PARTICIPANTS/MATERIALS, SETTING, METHODS: All women born between 1971 and 1997 who were identified with a PCOS diagnosis in the Swedish Patient Registry between 1 January 2001 and 31 December 2016 were included in the study population. Five controls per women with PCOS were randomly drawn from the Total Population Registry. The control women were born in the same year and living in the same municipality as the patient. The fecundity ratio (FR) was calculated by clustered Cox regression using a robust variance, adjusted for maternal birth period, country of birth and level of education.

    MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative probability of childbirth was 80.2% (95% CI, 79.5–80.9%) in women with PCOS and 78.2% (95% CI, 77.9–78.5%) in those without PCOS. Adjusted FR was 0.81 (95% CI, 0.80–0.82) for first childbirth and 0.58 (95% CI, 0.57–0.60) for first childbirth following a spontaneous pregnancy. The FR for second childbirth was 0.79 (95% CI, 0.77–0.80). Women with PCOS had more than one child less frequently than the comparison group. Within the PCOS group, early age at diagnosis, later birth year, Nordic country of origin and low educational level positively influenced the FR.

    LIMITATIONS, REASONS FOR CAUTION: Results are not adjusted for BMI, and time from intention to conceive to first childbirth could not be captured. Data on pregnancies, miscarriages or abortions and fertility treatment are unknown for women who did not give birth during the study period. Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes.

    WIDER IMPLICATIONS OF THE FINDINGS: While cumulative probability of childbirth is similar between groups, women with PCOS need longer time to achieve their first childbirth. Women with PCOS have a lower FR and give birth to fewer children per woman than women without PCOS. Early diagnosis of and information about PCOS may improve affected women’s reproductive potential.

    STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Swedish Society of Medicine. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests.

  • 15. Robb, A O
    et al.
    Mills, N L
    Smith, I B J
    Short, A
    Tura-Ceide, O
    Barclay, G R
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Critchley, H O D
    Newby, D E
    Denison, F C
    Influence of menstrual cycle on circulating endothelial progenitor cells2009In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 24, no 3, p. 619-625Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Endothelial progenitor cells (EPCs) are circulating mononuclear cells that participate in angiogenesis. The aim of this study was to determine the influence of the menstrual cycle on the number and function of EPCs, and to investigate their relationship with circulating concentrations of sex steroids and inflammatory mediators. METHODS: Ten healthy nulliparous, premenopausal, non-smoking women with regular menses were studied over a single menstrual cycle. Venepuncture was performed in the menstrual, follicular, peri-ovulatory and luteal phases. EPCs were quantified by flow cytometry (CD133(+)CD34(+)KDR(+) phenotype) and the colony-forming unit (CFU-EPC) functional assay. Circulating concentrations of estradiol, progesterone and inflammatory mediators (TNF-alpha, IL-6, sICAM-1 and VEGF) were measured by immunoassays. RESULTS: The numbers of CD133(+)CD34(+)KDR(+) cells were higher in the follicular phase (0.99 +/- 0.3 x 10(6) cells/l) compared with the peri-ovulatory phase (0.29 +/- 0.1 x 10(6) cells/l; P < 0.05). In contrast, the numbers of CFU-EPCs did not vary over the menstrual cycle. There were no correlations between EPCs and concentrations of either circulating sex steroids or inflammatory mediators. CONCLUSIONS: CD133(+)CD34(+)KDR(+) cells but not CFU-EPCs vary during the menstrual cycle. Our findings suggest a potential role for circulating EPCs in the normal cycle of physiological angiogenesis and repair of the uterine endometrium that is independent of circulating sex steroids or inflammatory mediators.

  • 16. Stukenborg, J. -B.
    et al.
    Alves-Lopes, J. P.
    Kurek, M.
    Albalushi, H.
    Reda, A.
    Keros, V.
    Töhönen, V.
    Bjarnason, R.
    Romerius, P.
    Sundin, M.
    Norén-Nyström, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Langenskiöld, C.
    Vogt, H.
    Henningsohn, L.
    Mitchell, R. T.
    Söder, O.
    Petersen, C.
    Jahnukainen, K.
    Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy2018In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, no 9, p. 1677-1683Article in journal (Refereed)
    Abstract [en]

    STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered. STUDY DESIGN, SIZE, DURATION: We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 +/- 3.8 [mean +/- SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 +/- 5.0 [mean +/- SD] years) from an internal biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes > 10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a nonmalignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 +/- 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 +/- 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 +/- 1.0, n = 8 and 4.1 +/- 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to nonalkylating agents were within recently published normative reference values. LIMITATIONS, REASONS FOR CAUTION: Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Forening For Barnasjukvard/Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Vare Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.

  • 17. Wirtberg, I
    et al.
    Möller, A
    Hogström, L
    Tronstad, S-E
    Lalos, Ann
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Life 20 years after unsuccessful infertility treatment2007In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 22, no 2, p. 598-604Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study explores the long-term experience of involuntary childlessness among 14 Swedish women 20 years after their infertility treatment. METHODS: In-depth interviews were conducted. RESULTS: The childlessness had had a strong impact on all the women’s lives and was for all a major life theme. The effects were experienced both on a personal level and on interpersonal and social levels. Half of the women were separated, and in all but one, sexual life was affected in negative and long-lasting ways. The effects of childlessness were especially increased at the time the study was conducted, as the women’s peer group was entering the ‘grandparent phase’. Many coped with their childlessness by caring for others, such as the children of friends or relatives, elderly parents or animals. CONCLUSION: These findings represent a small sample, but they point towards the need for developing models of counselling and support that stimulate self-reflection and strengthen personal resources and empowerment for individuals and couples experiencing involuntary childlessness.

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