Jan I. Olofsson

Full‐term newborn after repeated ovarian tissue transplants in a patient treated for Ewing sarcoma by sterilizing pelvic irradiation and chemotherapy

We report the first successful transplantation of cryopreserved ovarian cortical tissue into heavily irradiated tissues in a patient who had received sterilizing pelvic radiotherapy (54 Gy) and 40 weeks of intensive high‐dose chemotherapy for the treatment of Ewings sarcoma 14 years earlier. Repeated transplantation procedures were required to obtain fully functional follicular development. Enlargement of the transplants over time and increase of the size of the uterus were demonstrated on sequential ultrasonographic examinations. Eggs of good quality that could be fertilized in vitro were obtained only after a substantial incremental increase of the amount of ovarian tissue transplanted. Single embryo replacement resulted in a normal pregnancy and the birth of a healthy child by cesarean section at full‐term. No neonatal or maternal postoperative complications occurred. Women facing high‐dose pelvic radiotherapy should not be systematically excluded from fertility preservation options, as is currently the trend.

Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience.

The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries.

A randomized controlled trial of the GnRH antagonist ganirelix in Chinese normal responders: high efficacy and pregnancy rates

Gonadotropin-releasing hormone (GnRH) antagonists for controlled ovarian stimulation (COS) were only recently introduced into China. The efficacy and safety of the GnRH antagonist ganirelix was assessed in a multicenter, controlled, open-label study, in which Chinese women were randomized to either ganirelix (n = 113) or a long GnRH agonist protocol of triptorelin (n = 120). The primary end point was the amount of recombinant follicle-stimulating hormone (rFSH) required to meet the human chorionic gonadotropin criterion (three follicles ≥17 mm). The amount of rFSH needed was significantly lower for ganirelix (1272 IU) vs. triptorelin (1416 IU; P< 0.001). Ongoing pregnancy rates per started cycle were 39.8% (ganirelix) and 39.2% (triptorelin). Although both treatments were well tolerated, cancellation due to risk of ovarian hyperstimulation syndrome (OHSS) was less frequent with ganirelix (1.8%) than triptorelin (7.5%) (P = 0.06). Less rFSH was needed in the ganirelix protocol than the long GnRH agonist protocol, with fewer reported cases of OHSS and similar pregnancy rates.

Transgender men's experiences of fertility preservation: a qualitative study

STUDY QUESTION How do transgender men experience fertility preservation (FP) by cryopreservation of oocytes? SUMMARY ANSWER The procedures required prior to oocyte cryopreservation, such as hormonal ovarian stimulation and transvaginal ultrasound (TVS), have a negative impact on gender dysphoria as they are closely linked to the mens female assigned sex at birth, which is incompatible with their current status. WHAT IS KNOWN ALREADY Transgender persons often have high dissatisfaction with assigned sex-specific body features, such as the genital organs and androgen/oestrogen-responsive features. Thus, undergoing FP that requires genital-specific examinations, aimed at obtaining oocytes to cryopreserve, could be distressing. As no previous studies have investigated transgender mens experiences of FP involving cryopreservation of oocytes, little is known about their experience of the procedures. STUDY DESIGN, SIZE, DURATION This is a prospective study among adult transgender men referred for FP between March 2014 and December 2015. Individual in-depth qualitative interviews were conducted shortly after FP treatment. The interviews lasted between 62 and 111 min (mean 81 min) and were digitally recorded and transcribed verbatim. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were recruited on their first visit to the assisted reproduction clinic for reproductive counseling. There were 15 men, scheduled for FP, who chose to participate in the study (age 19–35); none had given birth and eight had a partner. Data were analyzed by thematic content analysis. MAIN RESULTS AND THE ROLE OF CHANCE The analysis resulted in three main categories: the journey to FP, reactions to the FP proceedings and strategies for coping. The referral for FP was an important part of the assessment and diagnosis and sometimes lined with frustrating waits and doubts. The reaction to the FP proceedings revealed that the genital examinations and the physical changes associated with discontinuation of testosterone or hormonal stimulation treatment triggered gender incongruence and dysphoria. However, for some, the negative expectations were not met. The participants used several coping strategies in order to manage the procedure, such as focusing on their reasons for undergoing FP, reaching out to friends and family for support and the cognitive approaches of not hating their body or using non-gendered names for their body parts. The results demonstrate the importance of contextual sensitivity during FP procedures. LIMITATIONS, REASONS FOR CAUTION The authors have strived to be reflective about their pre-understanding of the phenomenon. The majority of the participants resided in large urban areas; it is possible that transgender men living in rural areas have different experiences. WIDER IMPLICATIONS OF THE FINDINGS As the results are based on qualitative data from 15 transgender men, the results cannot readily be generalized to larger populations. However, the results are suggested to be applicable to other transgender men who want to undergo FP by cryopreservation of oocytes. The results show that transgender mens experience of FP places may elicit gender incongruence and gender dysphoria. However, health care personnel can alleviate distress by using a gender-neutral language and the preferred pronoun. Also, reassuringly, the men also have coping strategies of how to handle the situation. This knowledge is important to ensure adequate professional support for patients with gender dysphoria during FP. STUDY FUNDING/COMPETING INTEREST(S) Swedish Society of Medicine, Stockholm County Council and Karolinska Institutet (to K.A.R.-W.). TRIAL REGISTRATION NUMBER N/A.

Mycoplasma genitalium serum antibodies in infertile couples and fertile women

Objectives The association between Mycoplasma genitalium (M. genitalium) serum antibodies and infertility in women and men, as well as infertility subtypes, was investigated. Methods Stored serum was obtained from two patient cohorts: infertile couples (239 women and 243 men) attending a gynaecological outpatient clinic between October 1997 and February 2001 and 244 age-matched spontaneously pregnant women. An enzyme immunoassay was used to detect serum immunoglobulin G (IgG) antibodies to M. genitalium in these samples. Patients Chlamydia trachomatis seropositivity had been previously determined. Risks were calculated using multivariate logistic regression. Results M. genitalium serum IgG was more common among women of infertile couples (5.4%) than among fertile controls (1.6%) (OR (95%CI) 3.45 (1.10 to 10.75)), adjusting for C. trachomatis IgG (adjusted OR=3.00 (0.95 to 9.47)). Of the women with tubal factor infertility (TFI) 9.1% had M. genitalium IgG compared with 4.6% of women without TFI (OR=2.07 (0.60 to 7.05)); (AOR=1.20 (0.32 to 74.40)). In patients IgG positive to both microorganisms the OR for having TFI was increased (OR=4.86 (1.22 to 19.36)) compared with those positive to C. trachomatis IgG only (AOR=3.14 (1.58 to 6.20)). No associations were found with other infertility diagnoses. Only two men of the infertile couples were M. genitalium IgG positive (0.8%). Conclusions M. genitalium serum IgG was associated with infertility in women, however insignificant after adjustment for C. trachomatis IgG, but not with infertility subtypes within this study. M. genitalium IgG seroprevalence among men was very low and not associated with male factor infertility.

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

STUDY QUESTION Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? SUMMARY ANSWER 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. WHAT IS KNOWN ALREADY 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. STUDY DESIGN, SIZE, DURATION This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro 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. PARTICIPANTS/MATERIALS, SETTING, METHODS 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 = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <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. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER Not applicable.

Starting a uterus transplantation service: notes from a small island

from a small island H-K Tan, B-K Tan, L-K Tan, JI Olofsson, P Dahm-K€ ahler, M Br€ annstr€ om a Department of Obstetrics and Gynaecology, Singapore General Hospital, Singapore, Singapore b Department of Plastic, Reconstructive & Aesthetic Surgery, Singapore General Hospital, Singapore, Singapore c Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden d Division of Obstetrics and Gynecology, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden e Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, G€ oteborg, Sweden Correspondence: L-K Tan, Department of Obstetrics and Gynaecology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. Emails aetlk@yahoo.com; tan.lay.kok@singhealth.com.sg

A prospective investigation of perceived stress, infertility‐related stress, and cortisol levels in women undergoing in vitro fertilization: influence on embryo quality and clinical pregnancy rate

Women undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self‐reported perceived and infertility‐related stress and cortisol levels were associated with IVF cycle outcomes.

Postoperative AMH reduction is not associated with reduced fecundity two years following ovarian cyst surgery.

Abstract In a prospective study, we investigated the impact of anti-Müllerian hormone (AMH) changes following ovarian cyst surgery on the probability to achieve pregnancy and live birth. Women of reproductive age (n = 60) were included before surgery for benign ovarian cysts. Serum AMH concentrations were determined pre- and postoperative at 6 and 24 months. Information regarding pregnancy wish and attempts to conceive were obtained by a questionnaire. At the time of inclusion, 45/60 women reported desire of children. At six months, the levels of AMH decreased significantly in the whole group and further reduction was observed at two years (from 2.7 μg/L to 2.0 μg/L to 1.1 μg/L, respectively, p<  0.008), with a percentage reduction of 42.9%. At two-year follow-up, 36 women reported to have attempted to conceive and 18 achieved pregnancy (50%), with a live birth rate of 33%. The percentage change in AMH at two years did not differ significantly between the women who conceived versus those who did not (p = 0.117). Data reported herein demonstrate that the AMH reduction following ovarian cyst surgery is maintained two years after surgery; however, the postoperative AMH decrease that follows ovarian cyst surgery might not reduce the chances to achieve pregnancy.

Quality management systems for your in vitro fertilization clinic's laboratory: Why bother?

Several countries have in recent years introduced prescribed requirements for treatment and monitoring of outcomes, as well as a licensing or accreditation requirement for in vitro fertilization (IVF) clinics and their laboratories. It is commonplace for Assisted Reproductive Technology (ART) laboratories to be required to have a quality control system. However, more effective Total Quality Management systems are now being implemented by an increasing number of ART clinics. In India, it is now a requirement to have a quality management system in order to be accredited and to help meet customer demand for improved delivery of ART services. This review contains the proceedings a quality management session at the Indian Fertility Experts Meet (IFEM) 2010 and focuses on the creation of a patient-oriented best-in-class IVF laboratory.