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  • 1. Aittomäki, K
    et al.
    Wennerholm, U-B
    Bergh, C
    Selbing, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Hazekamp, J
    Nygren, K-G
    Safety issues in assisted reproduction technology. Should ICSI patients have genetic testing before treatment? A practical proposition to help patient information2004Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 19, nr 3, s. 472-476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 × 106/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.

  • 2.
    Bergh, Christina
    et al.
    Sahlgrenska Academy.
    Thurin Kjellberg, Ann
    Sahlgrenska Academy.
    Carlsson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Centrum för utvärdering av medicinsk teknologi.
    Randomized single versus double embryo transfer: Obstetric and paediatric outcome and a cost-effectiveness analysis2006Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 21, nr 1, s. 210-216Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Transfer of several embryos after IVF results in a high multiple birth rate associated with increased morbidity and high costs for the neonatal care. In a previous randomized trial we demonstrated that a single embryo transfer (SET) strategy, including one fresh single embryo transfer and, if no live birth, one additional frozen-thawed SET, resulted in a live-birth rate that was not substantially lower than after double embryo transfer (DET) but markedly reduced the multiple birth rate. Methods: We compared costs for maternal health care and productivity losses and paediatric costs for the SET and DET strategies. In addition, maternal and paediatric outcomes between the two groups were compared. Results: The SET strategy resulted in lower average total costs from treatment until 6 months after delivery. There were a few more deliveries with at least one live-born child in the DET group. The incremental cost per extra delivery in the DET alternative was high, €71 940. The rates of prematurely born and low birthweight children were significantly lower with the SET strategy. There were also markedly fewer maternal and paediatric complications in the SET group. Conclusions: The SET strategy is superior to the DET strategy, when number of deliveries with at least one live-born child, incremental cost-effectiveness ratio and maternal and paediatric complications are taken into consideration. The findings do not support continuing transfers of two embryos in this group of patients. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

  • 3.
    Borneskog, Catrin
    et al.
    Uppsala University.
    Skoog Svanberg, Agneta
    Uppsala University.
    Lampic, Claudia
    Karolinska Institute.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Relationship quality in lesbian and heterosexual couples undergoing treatment with assisted reproduction2012Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 27, nr 3, s. 779-786Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the major factors impacting on a couples relationship is the desire to have children. To many couples having a child is a confirmation of their love and relationship and a means to deepen and develop their intimate relationship. At the same time parental stress can impact on relationship quality. Relationship quality in lesbian couples is, currently, sparsely studied. The aim of the present study was to compare lesbian and heterosexual couples perceptions of their relationship quality at the commencement of assisted reproduction, and to relate this to background data such as educational level, having previous children and, for lesbian couples, the use of a known versus anonymous donor. less thanbrgreater than less thanbrgreater thanThe present study is part of the prospective longitudinal oSwedish study on gamete donation, including all fertility clinics performing donation treatment in Sweden. Of a consecutive cohort of 214 lesbian couples about to receive donor insemination and 212 heterosexual couples starting regular IVF treatment, 166 lesbian couples (78 response) and 151 heterosexual couples (71 response) accepted participation in the study. At commencement of assisted reproduction participants individually completed questionnaires including the instrument oENRICH, which is a standardized measure concerning relationship quality. less thanbrgreater than less thanbrgreater thanIn general, the couples rated their relationship quality as good, the lesbian couple better than the heterosexuals. In addition, the lesbian women with previous children assessed their relationship quality lower than did the lesbian woman without previous children. For heterosexual couples previous children did not influence their relationship quality. Higher educational levels reduced the satisfaction with the sexual relationship (P 0.04) for treated lesbian women, and enhanced the rating of conflict resolution for treated lesbian women (P 0.03) and their partners (P 0.02). Heterosexual women with high levels of education expressed more satisfaction with communication in their relationship (P 0.02) than did heterosexual women with lower educational levels. less thanbrgreater than less thanbrgreater thanIn this Swedish study sample of lesbian and heterosexual couples relationships, we found that they were generally well adjusted and stable in their relationships when starting treatment with donated sperm or IVF, respectively. However, where lesbian women had children from a previous relationship, it decreased relationship quality. For the heterosexual couples previous children did not affect relationship quality.

  • 4.
    Chaireti, Roza
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Medicinska akutkliniken.
    Gustafsson, K M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Bystrom, B
    Karolinska Institute, Sweden .
    Bremme, K
    Karolinska Institute, Sweden .
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Endogenous thrombin potential is higher during the luteal phase than during the follicular phase of a normal menstrual cycle2013Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 28, nr 7, s. 1846-1852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Do thrombin generation and haemostatic parameters differ during the two phases of the menstrual cycle? less thanbrgreater than less thanbrgreater thanTotal thrombin concentration is higher during the luteal phase compared with the follicular phase of the menstrual cycle. less thanbrgreater than less thanbrgreater thanThe coagulation cascade is affected by many variables, such as fluctuations in the levels of sex hormones. The studies on the variations in haemostatic parameters during the menstrual cycle have produced diverse results. less thanbrgreater than less thanbrgreater thanThrombin generation and selected haemostatic parameters (fibrinogen, factor II, factor VII, factor VIII, factor X, von Willebrand factor, antithrombin and D-dimer) were measured during the two phases of a normal menstrual cycle in 102 healthy women not taking any form of hormone medication. less thanbrgreater than less thanbrgreater thanThe study cohort consisted of 102 healthy women with regular menstrual cycles. Thrombin generation was measured by the calibrated automated thrombogram method. Progesterone and sex hormone-binding globulin were measured by chemiluminescence enzyme immunoassays. Estradiol was measured by a sensitive radioimmunoassay. Fibrinogen was measured by a clotting method, antithrombin was measured by a chromogenic method and factor II, factor VII, factor VIII, factor X, von Willebrand factor and D-dimer were measured by photometric methods. less thanbrgreater than less thanbrgreater thanIt was shown that the total amount of generated thrombin (Endogenous Thrombin Potential) was significantly higher during the luteal compared with the follicular phase (P 0.027). Factor X was significantly higher during the follicular phase (P 0.028). Progesterone exhibited significant associations (measured by the least squares regression analysis) with fibrinogen and factor X during the follicular phase (P 0.043 and P 0.033, respectively) and with factors II and VII during the luteal phase (P 0.034 and P 0.024, respectively). The validity of the results from the regression analysis was further confirmed by performing correlation analyses (Pearson correlation matrix) for haemostatic markers for the luteal and follicular phases (accepted correlation level 0.8). less thanbrgreater than less thanbrgreater thanThe wide confidence interval for the differences in endogenous thrombin potential during the two phases could imply that the size of the cohort may not be sufficient to fully evaluate the biological variations. Additionally, the haemostatic markers were not shown to have significant associations with thrombin generation, suggesting that the increased thrombin concentration during the luteal phase would be mediated by another mechanism, as yet unidentified. less thanbrgreater than less thanbrgreater thanThe associations between progesterone and the haemostatic markers, as shown for both phases of the menstrual cycle, suggest a previously unknown or undefined yet potentially significant role for progesterone in the coagulation system. However, it has been shown that the use of progestogen-only preparations does not affect the coagulation system, which is partly the reason why they are considered safe for women with thrombophilia or previous thrombotic event. Further studies are required in order to demonstrate whether our results can be extrapolated for synthetic progestins, which might have significant implication on the indications for their use. less thanbrgreater than less thanbrgreater thanThis study was supported by the Karolinska Institutet, Linkping University and the County Council of stergtland. The authors report no conflicts of interest.

  • 5.
    DeKeyser, Nicholas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Josefsson, Ann
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Bladh, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Finnström, Orvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Premature birth and low birthweight are associated with a lower rate of reproduction in adulthood: a Swedish population-based registry study2012Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 27, nr 4, s. 1170-1178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate if individuals born with sub-optimal birth characteristics have reduced probability of reproducing in adulthood. less thanbrgreater than less thanbrgreater thanUsing population-based registries, the authors included 522 216 males and 494 692 females born between 1973 and 1983 and examined their reproductive status as of 2006. Outcome measure was the hazard ratio (HR) of reproducing. Adjustments were made for socio-economic factors. less thanbrgreater than less thanbrgreater thanMales and females born very premature displayed a reduced probability of reproducing [HR 0.78, 95 confidence interval (CI): 0.700.86 for males; HR 0.81, CI: 0.750.88 for females]. Likewise for very low birthweight (HR 0.83, CI: 0.710.95 for males; HR 0.80, 95 CI: 0.720.89 for females). Individuals born large for gestational age (LGA) displayed no significant changes. Males born small for gestational age (SGA) had a 9 lower reproductive rate (CI: 0.890.94) and that reduction increased as the individuals aged. Women born SGA tended to start reproducing at an earlier age. less thanbrgreater than less thanbrgreater thanThe results suggest that being born with low birthweight, premature or SGA (for males) is associated with a reduced probability of reproducing as an adult. LGA shows no statistically significant relationship with future reproduction.

  • 6.
    Hazekamp, J
    et al.
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden Volvat Med Ctr, Oslo, Norway Karolinska Inst, Huddinge Hosp, Dept Obstet & Gynecol, S-10401 Stockholm, Sweden Vasteras Hosp, Dept Obstet & Gynecol, Linkoping, Sweden Linkoping Univ Hosp, Dept Obstet & Gynecol, S-58185 Linkoping, Sweden.
    Bergh, C
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden Volvat Med Ctr, Oslo, Norway Karolinska Inst, Huddinge Hosp, Dept Obstet & Gynecol, S-10401 Stockholm, Sweden Vasteras Hosp, Dept Obstet & Gynecol, Linkoping, Sweden Linkoping Univ Hosp, Dept Obstet & Gynecol, S-58185 Linkoping, Sweden.
    Wennerholm, UB
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden Volvat Med Ctr, Oslo, Norway Karolinska Inst, Huddinge Hosp, Dept Obstet & Gynecol, S-10401 Stockholm, Sweden Vasteras Hosp, Dept Obstet & Gynecol, Linkoping, Sweden Linkoping Univ Hosp, Dept Obstet & Gynecol, S-58185 Linkoping, Sweden.
    Hovatta, O
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden Volvat Med Ctr, Oslo, Norway Karolinska Inst, Huddinge Hosp, Dept Obstet & Gynecol, S-10401 Stockholm, Sweden Vasteras Hosp, Dept Obstet & Gynecol, Linkoping, Sweden Linkoping Univ Hosp, Dept Obstet & Gynecol, S-58185 Linkoping, Sweden.
    Karlstrom, PO
    Selbing, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Consideration of new strategies2000Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 15, nr 6, s. 1217-1219Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To maximize pregnancy rates, physicians who perform IVF, often transfer multiple embryos, which increases the multiple birth risk. Multiple birth infants are at significant risk for a number of adverse outcomes including preterm delivery, low birth weight, congenital malformations, fetal and infant deaths and long term morbidity and disability among survivors. Since the ultimate goal for an IVF treatment is the birth of a healthy infant, an important issue for all kinds of assisted reproductive technologies (ART) must be the reduction or elimination of multiple pregnancies. In this article, different strategies to avoid multiple births in ART are discussed.

  • 7. Hazekamp, J
    et al.
    Bergh, C
    Wennerholm, U-B
    Hovatta, O
    Karlström, PO
    Selbing, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Avoiding multipel pregnancies in ART. Consideration of new strategies.2000Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 15, s. 1217-1219Artikel i tidskrift (Refereegranskat)
  • 8.
    Hultling, C
    et al.
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Rosenlund, B
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Levi, Richard
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Fridström, M
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Sjöblom, P
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Hillensjö, T
    Department of Rehabilitation Medicine, Karolinska Institute, Stockholm, Sweden.
    Assisted ejaculation and in-vitro fertilization in the treatment of infertile spinal cord-injured men: the role of intracytoplasmic sperm injection.1997Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, nr 3, s. 499-502Artikel i tidskrift (Refereegranskat)
    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%.

  • 9.
    Isaksson, S.
    et al.
    Uppsala University, Sweden.
    Skoog-Svanberg, A.
    Uppsala University, Sweden.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Linell, L.
    Karolinska University Hospital, Sweden.
    Lampic, C.
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    It takes two to tango: information-sharing with offspring among heterosexual parents following identity-release sperm donation2016Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 31, nr 1, s. 125-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    How do heterosexual parents reason about and experience information-sharing with offspring following identity-release sperm donation? Sharing information about using donor-conception with offspring is a complex process at several levels, with the parents personal beliefs and the childs responses serving as driving or impeding forces for the information-sharing process. The overall view of disclosure in gamete donation has shifted from secrecy to openness, but there is still uncertainty among parents concerning how and when to tell the child about his/her genetic origin. Most research on donor-conceived families has focused on donation treatment under anonymous or known circumstances, and there is a lack of studies in settings with identity-release donations. A qualitative interview study among 30 parents following identity-release sperm donation treatment. Interviews were conducted from February 2014 to March 2015. The present study is part of the prospective longitudinal Swedish Study on Gamete Donation (SSGD), including all fertility clinics performing gamete donation in Sweden. A sample of participants in the SSGD, consisting of heterosexual parents with children aged 7-8 years following identity-release sperm donation, participated in individual semi-structured interviews. The analysis revealed one main theme: information-sharing is a process, with three subthemes; (i) the parent as process manager, (ii) the child as force or friction and (iii) being in the process. The first two subthemes were viewed as being linked together and their content served as driving or impeding forces in the information-sharing process. The fact that the study was performed within the context of the Swedish legislation on identity-release donation must be taken into consideration as regards transferability to other populations, as this may affect parents reasoning concerning their information-sharing with the child. The present findings highlight the role of the donor-conceived child in the information-sharing process and may contribute to develop counselling that increases parents confidence in handling childrens reactions to information about their genetic origin. Financial support from The Swedish Research Council, The Family Planning Fund in Uppsala and Ferring Pharmaceuticals. There are no conflicts of interest to declare. N/A.

  • 10.
    Isaksson, S
    et al.
    Uppsala University, Sweden .
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Skoog Svanberg, A
    Uppsala University, Sweden .
    Lampic, C
    Karolinska Institute, Sweden .
    Disclosure behaviour and intentions among 111 couples following treatment with oocytes or sperm from identity-release donors: follow-up at offspring age 14 years2012Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 27, nr 10, s. 2998-3007Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Do heterosexual parents of young children following oocyte donation (OD) and sperm donation (SD) tell or intend to tell their offspring about the way he/she was conceived? less thanbrgreater than less thanbrgreater thanFollowing successful treatment with oocytes or sperm from identity-release donors in Sweden, almost all heterosexual couples intend to tell their offspring about the way he/she was conceived and some start the information-sharing process very early. less thanbrgreater than less thanbrgreater thanAlthough the Swedish legislation on identity-release gamete donors has been in effect since 1985, there is a discrepancy between the behaviour of donor-insemination parents and the legal intention that offspring be informed about their genetic origin. The present study contributes data on a relatively large sample of oocyte and sperm recipient couples intended compliance with the Swedish legislation. less thanbrgreater than less thanbrgreater thanThe present study constitutes a follow-up assessment of heterosexual couples who had given birth to a child following treatment with donated oocytes. Data collection was performed during 20072011; participants individually completed a questionnaire when the child was between 1 and 4 years of age. less thanbrgreater than less thanbrgreater thanThe present study is part of the Swedish Study on Gamete Donation, a prospective longitudinal cohort study including all fertility clinics performing gamete donation in Sweden. For children conceived via OD, 107 individuals (including 52 couples and 3 individuals) agreed to participate (73 response). For children conceived via SD, the response rate was 70 (n 122 individuals, including 59 couples and 4 individuals). Mean age of participants was 34 years (SD 4.4) and they reported a high level of education. less thanbrgreater than less thanbrgreater thanThe majority of participants (78) planned to tell the child about the donation, 16 had already started the information-sharing process and 6 planned not to tell their child about the donation or were undecided. Many were unsure about a suitable time to start the disclosure process and desired more information about strategies and tools for information sharing. Agreement on disclosure to offspring within the couple was related to the quality of the partner relationship. less thanbrgreater than less thanbrgreater thanThere is a risk of selection bias, with gamete recipients preferring secrecy and non-disclosure declining study participation. The results may be regarded as partly generalizable to heterosexual couples with young children following treatment with gametes from legislatively mandated identity-release donors in an established donor programme. less thanbrgreater than less thanbrgreater thanStudy funding by Merck Serono, The Swedish Research Council and The Family Planning Fund in Uppsala. No conflicts of interest to declare.

  • 11.
    Jablonowska, Barbara
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Selbing, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Palfi, Miodrag
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Kjellberg, Svante
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Lindton, B
    Department of Obstetrics and Gynecology, Huddinge University Hospital, Huddinge, Sweden .
    Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study1999Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 14, nr 3, s. 838-841Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo.

  • 12.
    Lampic, C.
    et al.
    Karolinska Institute, Sweden.
    Skoog Svanberg, A.
    Uppsala University, Sweden.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Attitudes towards disclosure and relationship to donor offspring among a national cohort of identity-release oocyte and sperm donors2014Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 29, nr 9, s. 1978-1986Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY QUESTION: What are oocyte donors and sperm donors attitudes towards disclosure and relationship to donor offspring? SUMMARY ANSWER: Oocyte and sperm donors in an identity-release donor programme support disclosure to donor offspring and have overall positive or neutral attitudes towards future contact with offspring. WHAT IS KNOWN ALREADY: There is a global trend towards open-identity gamete donation with an increasing number of countries introducing legislation allowing only identifiable donors. While women and men who enrol in identity-release donor programmes accept that they may be contacted by donor offspring, there is limited knowledge of their attitudes towards disclosure to donor offspring and how they perceive their relationship to potential donor offspring. STUDY DESIGN, SIZE AND DURATION: The present study is part of the `Swedish study on gamete donation, a prospective cohort study including donors at all fertility clinics performing donation treatment in Sweden. During a 3-year period (2005-2008), donors were recruited consecutively and a total of 157 oocyte donors and 113 sperm donors (who did not donate to a specific `known couple) were included prior to donation. Participants in the present study include 125 female (80%) and 80 male donors (71%) that completed two follow-up assessments. PARTICIPANTS/MATERIALS, SETTINGS AND METHODS: Participants completed two postal questionnaires 2 months after donation and 14 months after donation. Attitudes towards disclosure to donor offspring were assessed with an established instrument. Perceptions of involvement with donor offspring and need for counselling was assessed with study-specific instruments. Statistical analyses were performed with non-parametric tests. MAIN RESULTS AND THE ROLE OF CHANCE: A majority of oocyte and sperm donors supported disclosure to donor offspring (71-91%) and had positive or neutral attitudes towards future contact with offspring (80-87%). Sperm donors reported a higher level of involvement with potential donor offspring compared with oocyte donors (P = 0.005). Few donors reported a need for more counselling regarding the consequences of their donation. LIMITATIONS, REASONS FOR CAUTION: While the multicentre study design strengthens external validity, attrition induced a risk of selection bias. In addition, the use of study-specific instruments that have not been psychometrically tested is a limitation. WIDER IMPLICATIONS OF THE FINDINGS: The positive attitudes towards disclosure to offspring of female and male identity-release donors are in line with previous reports of anonymous and known donors. While our results on donors general positive or neutral attitudes towards future contact with potential donor offspring are reassuring, a subset of donors with negative attitudes towards such contact warrants concern and suggests a need for counselling on long-term consequences of donating gametes. STUDY FUNDING: The `Swedish study on gamete donation was funded by the Swedish Research Council, the Swedish Council for Health, Working Life and Welfare, and the Regional Research Council in Uppsala-Orebro. There are no conflicts of interest to declare.

  • 13.
    Landfeldt, Erik
    et al.
    OptumInsight, Stockholm.
    Jablonowska, Barbara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Norlander, Elisabeth
    Merck Serono AB, Stockholm.
    Persdotter-Eberg, Karin
    Karolinska Universitetssjukhuset, Huddinge, Stockholm.
    Thurin-Kjellberg, Ann
    Sahgrenska Academy, Gothenburg University.
    Wramsby, Margaretha
    IVF Kliniken Cura, Malmö.
    Ström, Oskar
    Karolinska Institutet, Stockholm.
    Patient preferences for characteristics differentiating ovarian stimulation treatments2012Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 27, nr 3, s. 760-769Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Little is known concerning patient preferences for IVF treatments. The objective of this study was to elicit patient preferences for characteristics differentiating ovarian stimulation treatments.

    METHODS Women undergoing IVF were recruited from six clinics in Sweden between May 2010 and December 2010. Included patients completed a study questionnaire consisting of one contingent valuation (CV) question (with six different bids) and 16 conjoint analysis (CA) questions formulated as discrete choices between two hypothetical ovarian stimulation treatments (defined in terms of manufacturing method, method of administration, time required for administration, dose variability and hypothetical price). Patient preferences were derived using multinomial logit modelling.

    RESULTS The final study population consisted of 294 women (mean age of 35). Respondents were willing to pay €360 [95% confidence interval (CI): €340-€390] to receive FSH derived from DNA technology instead of highly purified extract from urine from post-menopausal women, €300 (95% CI: €280-€320) to administer the FSH using a prefilled injection pen instead of a conventional syringe, €30 (95% CI: €20-€40) per saved minute required for administration and €530 (95% CI: €500-€570) to reduce the dose variability from 10-20% to 1-2%(P< 0.001 for all estimates). The result from the CV was similar to the CA.

    CONCLUSIONS Women undergoing IVF place significant value on characteristics differentiating ovarian stimulation treatments. Product-specific aspects should be taken into account by decision-makers when discriminating between commercial gonadotrophins in clinical practice to align health-care decision-making with patient preferences and potentially improve the effectiveness of IVF interventions through enhanced patient satisfaction and treatment compliance. Preferences for treatment characteristics should also be considered in evaluations of ovarian stimulation products to capture their true value from a patient perspective.

  • 14.
    Lind, Tekla
    et al.
    Södersjukhuset, Sweden.
    Holte, Jan
    Carl von Linne Clin, Sweden; Uppsala Ctr Reprod Biol, Sweden.
    Olofsson, Jan I.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hadziosmanovic, Nermin
    Uppsala Univ, Sweden.
    Gudmundsson, Johannes
    Uppsala Univ Hosp, Sweden.
    Nedstrand, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Lood, Mikael
    Örebro Univ Hosp, Sweden.
    Berglund, Lars
    Uppsala Univ, Sweden.
    Rodriguez-Wallberg, Kenny
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study2018Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, nr 2, s. 238-247Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linn, Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linkoping University Hospital (D) and A-rebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control womens groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P =amp;lt; 0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = amp;lt; 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i. e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO.

  • 15.
    Lindau, Robert
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Bhai Mehta, Ratnesh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Lash, G. E.
    Guangzhou Women and Childrens Med Ctr, Peoples R China.
    Papapavlou, Georgia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Boij, Roland
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Cty Hosp Ryhov, Sweden.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Svensson Arvelund, Judit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Interleukin-34 is present at the fetal-maternal interface and induces immunoregulatory macrophages of a decidual phenotype in vitro2018Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, nr 4, s. 588-599Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY QUESTION: Is the newly discovered cytokine interleukin (IL)-34 expressed at the human fetal-maternal interface in order to influence polarization of monocytes into macrophages of a decidual immunoregulatory phenotype? SUMMARY ANSWER: IL-34 was found to be present at the fetal-maternal interface, in both fetal placenta and maternal decidua, and it was able to polarize monocytes into macrophages of a decidual phenotype. WHAT IS KNOWN ALREADY: IL-34 was shown to bind to the same receptor as macrophage-colony stimulating factor (M-CSF), which has an important immunomodulatory role at the fetal-maternal interface, for example by polarizing decidual macrophages to an M2-like regulatory phenotype. IL-34 is known to regulate macrophage subsets, such as microglia and Langerhans cells, but its presence at the fetal-maternal interface is unknown. STUDY DESIGN, SIZE, DURATION: The presence of IL-34 at the fetal-maternal interface was evaluated by immunohistochemistry (IHC) and ELISA in placental and decidual tissues as well as in isolated trophoblast cells and decidual stromal cells obtained from first trimester elective surgical terminations of pregnancy (n = 49). IL-34 expression was also assessed in third trimester placental biopsies from women with (n = 21) or without (n = 15) pre-eclampsia. The effect of IL-34 on macrophage polarization was evaluated in an in vitro model of blood monocytes obtained from healthy volunteers (n = 14). In this model, granulocyte macrophage-colony stimulating factor (GM-CSF) serves as a growth factor for M1-like polarization, and M-CSF as a growth factor for M2-like polarization. PARTICIPANTS/MATERIALS, SETTING, METHODS: First trimester placental and decidual tissues were obtained from elective pregnancy terminations. Placental biopsies were obtained from women with pre-eclampsia and matched controls in the delivery ward. Polarization of macrophages in vitro was determined by flow-cytometric phenotyping and secretion of cytokines and chemokines in cell-free supernatants by multiplex bead assay. MAIN RESULTS AND THE ROLE OF CHANCE: Our study shows that IL-34 is produced at the fetal-maternal interface by both placental cyto-and syncytiotrophoblasts and decidual stromal cells. We also show that IL-34, in vitro, is able to polarize blood monocytes into macrophages with a phenotype (CD14(high)CD163(+)CD209(+)) and cytokine secretion pattern similar to that of decidual macrophages. The IL-34-induced phenotype was similar, but not identical to the phenotype induced by M-CSF, and both IL-34-and M-CSF-induced macrophages were significantly different (P amp;lt; 0.05-0.0001 depending on marker) from GM-CSF-polarized M1-like macrophages. Our findings suggest that IL-34 is involved in the establishment of the tolerant milieu found at the fetal-maternal interface by skewing polarization of macrophages into a regulatory phenotype. LIMITATIONS, REASONS FOR CAUTION: Although it is clear that IL-34 is present at the fetal-maternal interface and polarizes macrophages in vitro, its precise role in vivo remains to be established. WIDER IMPLICATIONS OF THE FINDINGS: The recently discovered cytokine IL-34 is present at the fetal-maternal interface and has immunomodulatory properties with regard to induction of decidual macrophages, which are important for a healthy pregnancy. Knowledge of growth factors related to macrophage polarization can potentially be translated to treatment of pregnancy complications involving dysregulation of this process. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by grants from the Medical Research Council (Grant K2013-61X-22310-01-04), the Research Council of South-East Sweden (FORSS), and the County Council of Ostergotland, Sweden. No author has any conflicts of interest to declare.

  • 16.
    Lindh-Åstrand, Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Hoffmann, Mikael
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Järvstråt, Lotta
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Spetz, Anna-Clara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Hormone therapy might be underutilized in women with early menopause.2015Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, nr 4, s. 848-852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY QUESTION Are Swedish women age 40–44 years with assumed early menopause ‘undertreated’ by hormone therapy (HT)?

    SUMMARY ANSWER Many women with probable early menopause discontinue their HT after a short period of time. Thus, they fail to complete the recommended replacement up to age 51–52 years, the average age of menopause.

    WHAT IS KNOWN ALREADY Spontaneous early menopause occurs in ∼5% of women age 40–45 years. Regardless of the cause, women who experience hormonal menopause due to bilateral oophorectomy before the median age of spontaneous menopause are at increased risk of cardiovascular disease, neurological disease, osteoporosis, psychiatric illness and even death.

    STUDY DESIGN, SIZE, DURATION The study is descriptive, and epidemiological and was based on the use of national registers of dispensed drug prescriptions (HT) linking registers from the National Board of Health and Welfare and Statistics Sweden from 1 July 2005 until 31 December 2011.

    PARTICIPANTS/MATERIALS, SETTING, METHODS The study population consisted of 310 404 women, 40–44 years old on 31 December 2005 who were followed from 1 July 2005 until 31 December 2011.

    MAIN RESULTS AND THE ROLE OF CHANCE Only 0.9% of women 40–44 years old started HT during the study period. A majority of these women used HT <1 year.

    LIMITATIONS, REASONS FOR CAUTION We do not know the indications that led to the prescription of HT but assume that early onset of menopause was the main reason. Because of the study design—making a retrospective study of registers—we can only speculate on the reasons for most of the women in this group discontinuing HT. Another limitation of this study is that we have a rather short observation time. However, we have up to now only been able to collect and combine the data since July 2005.

    WIDER IMPLICATIONS OF THE FINDINGS As the occurrence of spontaneous early menopause in women age 40–45 is reported to be ∼5%, the fact that <1% of Swedish women age 40–44 are prescribed HT, and can be shown also to have had the medication dispensed at a pharmacy suggests an unexpectedly low treatment rate. Some women with early menopause may have used combined contraceptives as supplementation therapy, but in Sweden HT is the recommended treatment for early menopause so any such women are not following this recommendation. Women who experience early menopause are at increased risk for overall morbidity and mortality, and can expect to benefit from HT until they have reached at least the median age of spontaneous menopause. It is therefore important to individualize the information given these women and to convey new knowledge in this area to gynaecologists and physicians in general as well as the recommendation that women in this group continue HT at least until the average age for spontaneous menopause is reached.

  • 17.
    Nordqvist, S.
    et al.
    Uppsala University, Sweden .
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Lampic, C.
    Karolinska Institute, Sweden .
    Akerud, H.
    Uppsala University, Sweden .
    Elenis, E.
    Uppsala University, Sweden .
    Skoog Svanberg, A.
    Uppsala University, Sweden .
    Sexual orientation of women does not affect outcome of fertility treatment with donated sperm2014Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 29, nr 4, s. 704-711Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Is there a difference in fertility between heterosexual women and lesbians undergoing sperm donation? Women undergoing treatment with donated sperm are equally fertile regardless of sexual orientation. Lesbians have an increased prevalence of smoking, obesity, sexually transmitted diseases and, possibly, polycystic ovary syndrome, all factors known to affect fertility. Previous studies on sperm donation inseminations (D-IUI) show conflicting results regarding pregnancy outcome. This is a national study of 171 lesbians and 124 heterosexual women undergoing sperm donation both as D-IUI (lesbian n 438, heterosexual n 298) and as embryo transfers (ET) after IVF with donated sperm (lesbians n 225, heterosexuals n 230) during 20052010. All clinics in Sweden offering sperm donation recruited patients. Differences in patients medical history, treatment results and number of treatments to live birth were analyzed using independent samples t-test, Pearsons (2) test or Fishers exact probability test. 71.8 of heterosexuals and 69.0 of lesbians had a child after treatment. The mean number of treatments was 4.2 for heterosexual women and 3.9 for lesbians. The total live birth rate, regardless of treatment type, was 19.7 for heterosexuals and 19.5 for lesbians. For D-IUI, the live birth rate was 12.8 for heterosexuals and 16.0 for lesbians and the live birth rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7 for heterosexuals and 26.2 for lesbians. There were no differences in live birth rate between the groups for each of the different types of insemination stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH combined). Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2), uterine polyps (7.2) or previous children (11.3) than lesbians (smokers 2.8, P 0.03; polyps 1.8, P 0.03; child 2.5, P 0.003). This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation. Funding was granted by the Stiftelsen Familjeplaneringsfonden i Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of interest.

  • 18.
    Ponjaert-Kristoffersen, Ingrid
    et al.
    Vrije Universiteit, Brussels.
    Tjus, Tomas
    Psykologiska institutionen, Göteborgs universitet.
    Nekkebroek, J
    Vrije Universiteit, Brussels.
    Squires, Jane
    University of Oregon, USA.
    Verté, Dominique
    Vrije Universiteit, Brussels.
    Heimann, Mikael
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten.
    Bonduelle, Maryse
    Dutch-speaking University Hospital of Brussels.
    Palermo, Gianpiero
    Weill Medical College of Cornell University, NY, USA.
    Wennerholm, Ulla-Britt
    Sahlgrenska University Hospital, Göteborg.
    Psychological follow-up study of 5-year-old ICSI children2004Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 19, nr 12, s. 2791-2797Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The developmental outcomes of children born after ICSI are still a matter of concern. The purpose of the present study was to investigate psychological outcomes for 5-year-old children born after ICSI and compare these with outcomes for children born after spontaneous conception (SC). METHODS: Three hundred singleton children born after ICSI in Belgium, Sweden and the USA were matched by maternal age, child age and gender. Outcome measures included the Wechsler Preschool and Primary scales of intelligence (WPPSI-R), Peabody Developmental Motor Scales, Parenting Stress Index and Child Behaviour Checklist. RESULTS: Regarding cognitive development, no significant differences were found on WPPSI-R verbal and performance scales between ICSI and SC children. However, some differences were noted on subtests of the Performance Scale. ICSI children more often obtained a score below 1 SD of the mean on the subtests: Object Assembly, Block Design and Mazes (all P < 0.05). Significant differences by site (i.e. Belgium, Sweden and New York) were found on subtests related to parenting stress, child behaviour problems and motor development (all P < 0.05). These findings can probably be explained by variables other than conception mode, such as cultural differences and selection bias. CONCLUSIONS: Although the finding that a higher proportion of ICSI children obtained scores below the cut-off on some of the visual–spatial subscales of the WPPSI-R warrants further investigation, ICSI does not appear to affect the psychological well-being or cognitive development at age 5.

  • 19.
    Stukenborg, J. -B.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Alves-Lopes, J. P.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Kurek, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Albalushi, H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Sultan Qaboos Univ, Oman.
    Reda, A.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Katholieke Univ Leuven, Belgium.
    Keros, V.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Tohonen, V.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bjarnason, R.
    Landspitali Univ Hosp, Iceland; Univ Iceland, Iceland.
    Romerius, P.
    Lund Univ, Sweden.
    Sundin, M.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nystrom, U. Noren
    Umea Univ, Sweden.
    Langenskiold, C.
    Queen Silvia Childrens Hosp, Sweden.
    Vogt, Hartmut
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Henningsohn, L.
    Karolinska Inst, Sweden.
    Mitchell, R. T.
    Univ Edinburgh, Scotland; Edinburgh Royal Hosp Sick Children, Scotland.
    Soder, O.
    Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Petersen, C.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jahnukainen, K.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Helsinki, Finland.
    Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy2018Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, nr 9, s. 1677-1683Artikel i tidskrift (Refereegranskat)
    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 non-malignant 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 non-alkylating 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 Förening För Barnasjukvård/ Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Väre 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.

  • 20.
    Sydsjö, Gunilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ekholm, Katarina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi.
    Lampic, C
    Attitudes towards gamete donation among Swedish gynaecologists and obstetricians2008Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 23, nr 4, s. 904-911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Assisted reproductive technology (ART) legislation in Sweden has undergone a gradual transformation from being fairly restrictive when first introduced to becoming more permissive in recent years. Regarding gamete donation, Sweden became the first country to pass legislation about disclosure by establishing a child's right to find out the identity of the gamete donor once the child has reached maturity. Our aim was to investigate attitudes towards gamete donation among Swedish gynaecologists and obstetricians. METHODS: A questionnaire was mailed to all gynaecologists and obstetricians listed from a commercial register of all working in Sweden. Among 1230 eligible gynaecologists/obstetricians, 854 (69%) answered the questionnaire. RESULTS: In general, the majority of Swedish gynaecologists/obstetricians had positive attitudes towards gamete donation. Although a majority advocated openness regarding informing the child that he or she was conceived by making use of gamete donation, ∼40% opposed allowing the child to receive any information about the donor when the child has reached maturity. Even though Swedish legislation has allowed sperm donation to lesbian couples since July 2005, one-third of the gynaecologists/obstetricians opposed donation to lesbians. CONCLUSIONS: The results indicate that the gynaecologists'/obstetricians' negative attitudes towards disclosure may influence patients' ability to discuss their thoughts and feelings about donation. This may also have a negative impact on donor recruitment as well as on the extent of methods made accessible within ART. © The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

  • 21.
    Sydsjö, Gunilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Ekholm, Katarina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi.
    Wadsby, Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Barn- och ungdomspsykiatri.
    Kjellberg, Svante
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Sydsjö, Adam
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Relationships in couples after failed IVF treatment: A prospective follow-up study2005Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 20, nr 7, s. 1952-1957Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are few studies of couples that analyse satisfaction with treatment, adoption plans and relationships in couples after unsuccessful IVF. Methods: ENRICH marital inventory was used to describe marital dynamics and to gain information about treatment and adoption plans. A specially designed questionnaire was used. Of the 51 couples without previous children who were asked to participate after their first failed IVF cycle, 45 participated. The next stage of the study was carried out when the couples had reached the 6 months point after the first IVF cycle, and the last stage after the couples had been through one to three treatments, 1 1/2 years after the last treatment. Results: The couples displayed a stable relationship from the start as well as 1 year after the last IVF cycle. The vast majority of the couples had decided to go through with an adoption. Seventy-three percent of the women were interested in more IVF treatment compared to 33% of the men. Conclusion: The stresses associated with IVF treatment did not have a negative impact on the couples' appreciation of their relationships during and after the treatment period. After treatment had been completed, the couples seemed to have reoriented themselves toward other solutions to childlessness.

  • 22.
    Sydsjö, Gunilla
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Skoog Svanberg, A.
    Uppsala University.
    Lampic, C.
    Karolinska Institute.
    Jablonowska, Barbara
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi.
    Relationships in IVF couples 20 years after treatment2011Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 26, nr 7, s. 1836-1842Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Involuntary childlessness is a psychological and social dilemma for at least one but usually both members of the childless couples and is thought to have a lifelong impact on many of these couples. Studies of the long-term effects are scarce and the participation rate in published studies is generally very low. We therefore intended to analyse relationships and family structure in couples 20-23 years after the women in these couples had received IVF treatment. METHODS: The data are drawn from answers from 788 individuals-81% of the individuals treated. ENRICH has been used to analyse the relationships in those couples who stated that they have remained a couple since their IVF treatment. In total, 412 men and women (206 couples) answered the ENRICH inventory. A total of 14 men and 137 women answered the ENRICH, without their spouse answering the inventory. RESULTS: We found that the majority of all couples show a stable relationship 20 years or more after the date of IVF treatment. However, the group of couples who remained childless (9.2% of the total study population) during the 20 years following the IVF treatment differ from the majority on the subscale Children and Parent measuring aspects on attitudes and feelings about having and raising children. Another difference seen in the couples that were childless was that men scored significantly higher on Conflict resolution and the couples had a higher average score on positive agreement on the issues on Communication indicating a skill in communication in the relationship and also an agreement that they are communicating well. CONCLUSIONS: We found that the majority of IVF couples (90.8%) who had been treated similar to 20 years prior to follow-up had added at least one biological or adopted child to the family during that time. The relationships in couples who had continued to stay together during that period were generally described as being good, whether the couples had become parents or not.

  • 23.
    Sydsjö, Gunilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Wadsby, Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Barn- och ungdomspsykiatri.
    Kjellberg, Svante
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sydsjö, Adam
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Relationships and parenthood in couples after assisted reproduction and in spontaneous primiparous couples: A prospective long-term follow-up study2002Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 17, nr 12, s. 3242-3250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study was to analyse relationships and parenthood in primiparous IVF couples and spontaneous primiparous couples. Method: In total, 110 consecutive IVF couples were studied. The control group was matched for women's age and selected out of the total spontaneous pregnant population in the study area. Questionnaires and semi-structured telephone interviews were used to gain information about sociodemographic data, couples' relationships, and the children's health, temperament and behaviour. Obstetrical variables concerning the course and outcome of pregnancy and delivery as well as the health status of the new-borns were obtained from standardized antenatal care and delivery files. Results: There weere no differences concerning gestational age, mode of delivery or neonatal health between the two groups. The IVF couples were more stable over time - from pregnancy until the child was 1 year old - in their relationship, while the control group experienced a decrease in marital satisfaction. The children in the IVF group were assessed by their parents as being more regular/habitual, sensitive and manageable than the control children. Conclusion: The differences present between the groups were in favour of the IVF families, and the effects of the infertility crisis were not notable when the children were 1 year old.

  • 24.
    Thurin, A.
    et al.
    Department of Reproductive Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
    Hardarson, T.
    Fertility Centre of Scandinavia, Carlanderska Hospital, Göteborg, Sweden.
    Hausken, J.
    Fertility Clinic, Haugesund Hospital, Haugesund, Norway.
    Jablonowska, Barbara
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin.
    Lundin, K.
    Department of Reproductive Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
    Pinborg, A.
    Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Bergh, C.
    Department of Reproductive Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
    Predictors of ongoing implantation in IVF in a good prognosis group of patients2005Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 20, nr 7, s. 1876-1880Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study was to investigate whether, in a large randomized trial, it is possible to identify specific maternal and/or embryo variables that could independently correlate with ongoing implantation in IVF/ICSI. Methods: In a Scandinavian study, 661 women were randomized to elective single embryo transfer or double embryo transfer. Women aged <36 years undergoing their first or second IVF cycle and with at least two good quality embryos were eligible. Only one cycle per subject was included. In the present study, cycles with 0 or 100% ongoing implantation (n = 520) were analysed regarding maternal and embryo variables. Results: In this selected study group, the ongoing implantation rate was 195/734 (26.6%). In the univariate analysis, first IVF cycle, conventional IVF as fertilization method and 4-cell embryos showed a statistically higher ongoing implantation rate than did second IVF cycle, ICSI and non-4-cell embryos. In the multivariate analysis the same variables correlated independently to ongoing implantation. In addition, ovarian sensitivity correlated independently to ongoing implantation. Conclusion: This information should be used when selecting the number of embryos for transfer with the overall aim to reduce the rate of multiple births while maintaining a satisfactory birth rate. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

  • 25.
    Tong, Mancy
    et al.
    University of Auckland, New Zealand.
    Kleffmann, Torsten
    University of Otago, New Zealand.
    Pradhan, Shantanu
    University of Auckland, New Zealand.
    Johansson, Caroline L.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. University of Auckland, New Zealand.
    DeSousa, Joana
    Auckland City Hospital, New Zealand.
    Stone, Peter R.
    University of Auckland, New Zealand; Auckland City Hospital, New Zealand.
    James, Joanna L.
    University of Auckland, New Zealand.
    Chen, Qi
    University of Auckland, New Zealand.
    Chamley, Larry W.
    University of Auckland, New Zealand.
    Proteomic characterization of macro-, micro- and nano-extracellular vesicles derived from the same first trimester placenta: relevance for feto-maternal communication2016Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 31, nr 4, s. 687-699Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY QUESTION: What proteins are carried by extracellular vesicles (EVs) released from normal first trimester placentae? SUMMARY ANSWER: One thousand five hundred and eighty-five, 1656 and 1476 proteins were characterized in macro-, micro-and nano-vesicles, respectively, from first trimester placentae, with all EV fractions being enriched for proteins involved in vesicle transport and inflammation. WHAT IS KNOWN ALREADY: Placental EVs are being increasingly recognized as important mediators of both healthy and pathological pregnancies. However, current research has focused on detecting changes in specific proteins in particular fractions of vesicles during disease. This is the first study to investigate the full proteome of different-sized fractions of EVs from the same first trimester placenta and highlights the differences/similarities between the vesicle fractions. STUDY DESIGN, SIZE, DURATION: A well-established ex vivo placental explant culture model was used to generate macro-, micro-and nano-vesicles from 56 first trimester placentae. Vesicle fractions were collected by differential ultracentrifugation, quantified and characterized. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placental macro-, micro-and nano-vesicles were characterized by microscopy, dynamic light scattering and nanoparticle tracking analysis. The proteome of each EV fraction was interrogated using liquid chromatography-coupled tandem mass spectrometry. Results were validated by semi-quantitative western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1585, 1656 and 1476 proteins were identified in macro-, micro-and nanovesicles, respectively. One thousand one hundred and twenty-five proteins were shared between all three fractions while up to 223 proteins were unique to each fraction. Gene Ontology pathway analysis showed an enrichment of proteins involved in vesicle transport and inflammation in all three fractions of EVs. The expression levels of proteins involved in internalization of vesicles (annexin V, calreticulin, CD31, CD47), the complement pathway [C3, decay-accelerating factor (DAF), membrane cofactor protein (MCP), protectin] and minor histocompatibility antigens [ATP-dependent RNA helicase (DDX3), ribosomal protein S4 (RPS4)] were different between different-sized EVs. LIMITATIONS, REASONS FOR CAUTION: This study is largely hypothesis-generating in nature. It is important to validate these findings using EVs isolated from maternal plasma and the function of the different EV fractions would need further investigation. WIDER IMPLICATIONS OF THE FINDINGS: Our results support the concept that various EV factions can interact with different maternal cells and have unique effects to mediate feto-maternal communication during early pregnancy. This study also provides a list of candidate proteins, which may inform the identification of robust markers that can be used to isolate placental vesicles from the maternal blood in the future.

  • 26.
    Vikström, Josefin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Josefsson, Ann
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa.
    Hammar, Mats
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa.
    Bladh, Marie
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa.
    Sydsjö, Gunilla
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa.
    Risk of postpartum psychosis after IVF treatment: a nationwide case-control study2017Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 32, nr 1, s. 139-146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY QUESTION: Is the risk of postpartum psychosis (PPP) increased in women who give birth after IVF treatment compared to after spontaneous conception? SUMMARY ANSWER: The risk of PPP is not higher in the group of women who give birth after IVF treatment compared with women who give birth after spontaneous conception. WHAT IS KNOWN ALREADY: Women who conceive using IVF treatment can experience higher levels of pregnancy-specific distress and are at increased risk of pre-eclampsia, an immune-related condition which in turn has been linked to PPP, as well as other pregnancy and delivery complications, which also serve as PPP risk factors. It is not known whether the risk of PPP is increased in women who have conceived using IVF treatment. STUDY DESIGN, SIZE, DURATION: A nationwide, register-based, case-control study of all primiparous women who had given birth after IVF treatment between 1988 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information about 10 412 women was collected from the Swedish IVF register. A control group of women who had given birth after spontaneous conception was selected from the Swedish Medical Birth Register (n = 18 624). PPP diagnoses, identified using ICD-10 diagnostic codes F20-31 and F531 the first year postpartum, were collected from the National Patient Register. Associations between PPP and IVF/spontaneous conception were evaluated using chi-square tests and logistic regression analyses while controlling for known risk factors of PPP. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in PPP prevalence between the IVF group and the control group (0.3%, n = 29 versus 0.4%, n = 77) in the chi-square analysis (P = 0.169) or the multiple logistic regression analyses (P = 0.646; odds ratio (OR): 1.178; 95% CI: 586-2.365). No associations between pregnancy or delivery complications and PPP were found. A history of any psychiatric disorder (P amp;lt; 0.001; OR = 40.7; 95% CI = 23.9-69.5), or specifically a psychotic (P amp;lt; 0.001; OR = 324.1; 95% CI = 131.3-800.0), bipolar (P amp;lt; 0.001; OR = 516.1; 95% CI = 264.3-1008.1), depressive (P amp;lt; 0.001; OR = 27.5; 95% CI = 16.2-46.5), anxiety (P amp;lt; 0.001; OR = 12.9; 95% CI = 7.4-22.6) or personality disorder (P amp;lt; 0.001; OR = 27.3; CI = 11.8-63.0), all significantly increased the risk of PPP. LIMITATIONS REASONS FOR CAUTION: PPP is a rare condition, hence the number of individuals was small. Since all women for whom information was available from all registers were included, it was not possible to further increase the power of the study using this design. WIDER IMPLICATIONS OF THE FINDINGS: Since this study is the first to examine risk of PPP after IVF treatment, more studies are needed to verify these results. The generalizability is restricted to primiparous women in western countries. This study confirms the results of previous studies in showing a history of mental illness to be the major risk factor for PPP.

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