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1.
Int Breastfeed J ; 19(1): 18, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38462609

ABSTRACT

BACKGROUND: We present a case of non-puerperal induced lactation in transgender woman. Medical literature on lactation induction for transgender women is scarce, and the majority of literature and protocols on lactation induction is based on research in cisgender women. Healthcare professionals may lack the precise knowledge about lactation induction and may therefore feel insecure when advice is requested. Subsequently, there is a rising demand for guidelines and support. METHODS: Patient medical record was consulted and a semi-structured interview was conducted to explore the motive for lactation induction, the experience of lactation induction, and to gather additional information about the timeline and course of events. CASE PRESENTATION: In this case a 37-year-old transgender woman, who was under the care of the centre of expertise on gender dysphoria in Amsterdam, and in 2020 started lactation induction because she had the wish to breastfeed her future infant. She was in a relationship with a cisgender woman and had been using gender affirming hormone therapy for 13 years. Prior to initiating gender affirming hormone therapy she had cryopreserved her semen. Her partner conceived through Intracytoplasmic Sperm Injection, using our patient's cryopreserved sperm. To induce lactation, we implemented a hormone-regimen to mimic pregnancy, using estradiol and progesterone, and a galactogogue; domperidone. Our patient started pumping during treatment. Dosage of progesterone and estradiol were significantly decreased approximately one month before childbirth to mimic delivery and pumping was increased. Our patient started lactating and although the production of milk was low, it was sufficient for supplementary feeding and a positive experience for our patient. Two weeks after birth, lactation induction was discontinued due to suckling problems of the infant and low milk production. CONCLUSIONS: This case report underlined that lactation induction protocols commonly used for cisgender women are also effective in transgender women. However, the amount of milk produced may not be sufficient for exclusive nursing. Nevertheless, success of induced lactation may be attributed to its importance for parent-infant bonding, rather than the possibility of exclusive chestfeeding.


Subject(s)
Lactation , Transgender Persons , Adult , Female , Humans , Male , Breast Feeding , Estradiol , Progesterone , Semen
2.
Cell Rep Med ; 5(3): 101440, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38402622

ABSTRACT

Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy. Histological signs of recent ovulatory activity, including the presence of ovulatory follicles, corpus luteum, and corpus albicans, are observed in 17 of 52 individuals (33%). This is not significantly correlated to the duration, testosterone serum levels, or type of testosterone used. These results suggest that amenorrhea does not equal anovulation in transmasculine people on adequate testosterone therapy, emphasizing the importance of contraception for people who engage in sexual activity that can result in pregnancy.


Subject(s)
Amenorrhea , Testosterone , Pregnancy , Female , Humans , Testosterone/therapeutic use , Amenorrhea/drug therapy , Ovulation
3.
Int J Mol Sci ; 24(23)2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38069168

ABSTRACT

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.


Subject(s)
Follicular Atresia , Ovary , Humans , Female , Ovarian Follicle , Granulosa Cells , Theca Cells
4.
Acta Obstet Gynecol Scand ; 102(9): 1159-1175, 2023 09.
Article in English | MEDLINE | ID: mdl-37345445

ABSTRACT

INTRODUCTION: Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment. MATERIAL AND METHODS: We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42021214093. RESULTS: 1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group. CONCLUSIONS: Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.


Subject(s)
Abortifacient Agents, Nonsteroidal , Pregnancy, Ectopic , Pregnancy, Tubal , Pregnancy , Humans , Female , Methotrexate/therapeutic use , Watchful Waiting , Pregnancy, Tubal/drug therapy , Pregnancy, Ectopic/drug therapy , Chorionic Gonadotropin , Abortifacient Agents, Nonsteroidal/therapeutic use , Retrospective Studies
5.
Reprod Biomed Online ; 47(1): 94-101, 2023 07.
Article in English | MEDLINE | ID: mdl-37095040

ABSTRACT

RESEARCH QUESTION: What are the outcomes and experiences of oocyte vitrification treatment in trans masculine individuals (TMI) before and after testosterone use? DESIGN: This retrospective cohort study was conducted at the Amsterdam UMC in the Netherlands between January 2017 and June 2021. The TMI who had completed an oocyte vitrification treatment were consecutively approached for participation. Informed consent was provided by 24 individuals. Participants (n = 7) who initiated testosterone therapy were advised to stop 3 months before stimulation. Demographic characteristics and oocyte vitrification treatment data were retrieved from medical records. Evaluation of the treatment was collected via an online questionnaire. RESULTS: The median age of participants was 22.3 years (interquartile range 21.1-26.0) and mean body mass index was 23.0 kg/m2 (SD 3.2). After ovarian hyperstimulation, a mean of 20 oocytes (SD 7) were retrieved and a mean of 17 oocytes (SD 6) could be vitrified. Aside from a lower cumulative FSH dose, there were no significant differences between the prior testosterone users and testosterone naïve TMI. The overall satisfaction of oocyte vitrification treatment in participants was high. Hormone injections were considered the most strenuous part of treatment by 29% of participants, closely followed by oocyte retrieval (25%). CONCLUSIONS: No difference in response to ovarian stimulation was found for oocyte vitrification treatment between the prior testosterone users and testosterone naïve TMI. The questionnaire identified hormone injections as the most burdensome aspect of oocyte vitrification treatment. This information can be used to improve gender sensitive fertility counselling and fertility treatment strategies.


Subject(s)
Fertility Preservation , Vitrification , Cryopreservation/methods , Fertility Preservation/methods , Retrospective Studies , Oocytes/physiology , Oocyte Retrieval , Testosterone/therapeutic use
6.
Cell Rep Med ; 4(1): 100858, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36652919

ABSTRACT

Increasing numbers of transgender individuals are presenting for gender-affirming medical care. For trans women, gender-affirming hormone therapy (GAHT) promotes feminization but also inhibits spermatogenesis. There is a common untested assumption that this inhibition is permanent, resulting in infertility. In this longitudinal study, we report the recovery of viable spermatozoa in nine trans women who stopped GAHT for reproductive purposes. Our preliminary findings suggest that the negative impact of GAHT on spermatogenesis can be reversed, casting doubt on previous claims that GAHT in trans women inevitably leads to permanent infertility. Larger studies are needed to confirm our findings, which have implications not only for fertility counseling and the reproductive options of transgender individuals but also efforts to restrict access to GAHT based on fertility grounds.


Subject(s)
Infertility , Transgender Persons , Male , Female , Humans , Longitudinal Studies , Spermatogenesis , Hormones
7.
Int J Transgend Health ; 24(1): 7-25, 2023.
Article in English | MEDLINE | ID: mdl-36713139

ABSTRACT

Background: Hormonal treatments and surgical interventions practiced with the aim to affirm gender identity in transgender and gender diverse patients may impact their future reproductive ability, family building, and family planning options. Whereas it is recommended by international guidelines to discuss the potential risks of infertility and to present fertility preservation (FP) options to transgender individuals and their families prior to initiating any of these treatments, many barriers still remain. Further, transgender and gender diverse individuals often experience barriers to accessing contraception, abortion, pre-conception care, and comprehensive perinatal care. Aims: In this review we summarize the current literature on reproductive healthcare issues reported in transgender people including fertility issues, fertility preservation (FP), contraception, pregnancy and lactation and perinatal health. Methods: A narrative literature search of major databases (Pubmed, Medline, PsycInfo, Google Scholar, Web of Science) was conducted. Given the paucity and heterogeneity of studies, summative review tactics were not available. The literature was critically reviewed by international experts in the field with focus on the impact of gender-affirming medical interventions on future fertility, current FP options and reproductive health issues in transgender people. Results: The current literature supports that transgender and gender diverse individuals may wish to have genetically related children in the future, rendering the issue of FP relevant to this patient group. The cryopreservation of mature gametes is an efficacious option for FP for post-pubertal adolescents and adults. It is recommended to discuss these options at time of planning for gender-affirming hormonal therapy (GAHT) or engaging with other gender-affirming procedures that can limit future fertility. Discontinuation of GAHT may allow individuals to undergo FP later, but data are limited and there is the concern of symptoms and consequences of stopping GAHT. For pre-pubertal and early pubertal children, FP options are limited to the cryopreservation of gonadal tissue. At present the tissue can become functional only after re-transplantation, which might be undesirable by transgender individuals in the future. Preconception counseling, prenatal surveillance, perinatal support, contraceptive, and pregnancy termination related healthcare need to be meaningfully adapted for this patient population, and many knowledge gaps remain. Discussion: Specialized FP reproductive healthcare for transgender and gender diverse individuals is in early evolution. Research should be conducted to examine effects of medical interventions on fertility, timing of FP, gamete preservation and outcome of the fertility treatments. Strategies to inform and educate transgender and gender diverse patients can lead to optimization of reproductive care and counseling and decision making of FP for this population.

8.
AJOG Glob Rep ; 3(1): 100143, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36691399

ABSTRACT

BACKGROUND: There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined. OBJECTIVE: This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management. STUDY DESIGN: We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth. RESULTS: Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P=.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P=.01) after a curettage, and 6 months (interquartile range, 4-15; P=.03) after a laparoscopic niche resection. CONCLUSION: Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies.

9.
Front Endocrinol (Lausanne) ; 13: 936765, 2022.
Article in English | MEDLINE | ID: mdl-35966050

ABSTRACT

Current strategies for fertility preservation include the cryopreservation of embryos, mature oocytes or ovarian cortical tissue for autologous transplantation. However, not all patients that could benefit from fertility preservation can use the currently available technology. In this regard, obtaining functional mature oocytes from ovarian cortical tissue in vitro would represent a major breakthrough in fertility preservation as well as in human medically assisted reproduction. In this study, we have used a microfluidics platform to culture cryopreserved-thawed human cortical tissue for a period of 8 days and evaluated the effect of two different flow rates in follicular activation and growth. The results showed that this dynamic system supported follicular development up to the secondary stage within 8 days, albeit with low efficiency. Surprisingly, the stromal cells in the ovarian cortical tissue were highly sensitive to flow and showed high levels of apoptosis when cultured under high flow rate. Moreover, after 8 days in culture, the stromal compartment showed increase levels of collagen deposition, in particular in static culture. Although microfluidics dynamic platforms have great potential to simulate tissue-level physiology, this system still needs optimization to meet the requirements for an efficient in vitro early follicular growth.


Subject(s)
Fertility Preservation , Ovarian Follicle , Cryopreservation/methods , Female , Fertility Preservation/methods , Humans , Microfluidics , Oocytes
10.
Reprod Biomed Online ; 45(5): 1033-1038, 2022 11.
Article in English | MEDLINE | ID: mdl-35918245

ABSTRACT

RESEARCH QUESTION: What is the endometrial thickness of endometrium exposed to testosterone in transmasculine people compared with unexposed endometrium in cisgender women as determined by transvaginal ultrasound (TVU)? DESIGN: Single centre, cross-sectional cohort study conducted the Centre of Expertise on Gender Dysphoria in Amsterdam. Between 2013 and 2015, transmasculine people scheduled for gender affirming surgery (GAS) were included in this study after they provided informed consent. They were undergoing gender affirming hormone therapy (testosterone) for at least 1 year. Endometrial thickness (mm) was measured by TVU in transmasculine people, immediately before their GAS while under general anaesthesia. Cisgender control women from the general population underwent the exact same TVU measurements in an outpatient clinical setting on cycle days 2-5. RESULT: Fifty-one transmasculine people and 77 controls were included. The mean duration of testosterone use was 30.2 months (SD 8.8). Endometrial thickness was significantly lower in transmasculine people compared with cisgender women: median 3.9 mm (interquartile range [IQR] 2.8-5.1) and 4.9 mm (IQR 4.0-6.3), respectively (P < 0.001), after correcting for confounding factor (current gonadotrophin releasing hormone agonist use). CONCLUSIONS: Endometrial thickness in transmasculine people exposed to testosterone is significantly lower compared with cisgender women without testosterone exposure. These results suggest an absence of endometrial proliferation by exogenous testosterone.


Subject(s)
Testosterone , Transgender Persons , Humans , Female , Cross-Sectional Studies , Gender Identity , Endometrium/diagnostic imaging , Ultrasonography
11.
Am J Obstet Gynecol ; 226(3): 390.e1-390.e10, 2022 03.
Article in English | MEDLINE | ID: mdl-34688596

ABSTRACT

BACKGROUND: Transgender women (people assigned male genders at birth with female gender identities) can choose to cryopreserve semen before their medical transition, to retain the possibility to parent genetically related offspring later in life. Our previous retrospective study showed that semen quality in transgender women was decreased compared with the general population. The etiology of this impaired semen quality remains largely unknown. However, impaired semen quality might be related to habitual behavior more typically observed in transgender women, for example, the desire to hide their testicles because of genital dysphoria. Therefore, we decided to conduct a consecutive study with prospectively obtained data on behavior and lifestyle in transgender women. OBJECTIVE: This study aimed to study the influence of a low ejaculation frequency, wearing tight undergarments, and bringing the testes in the inguinal position (tucking) on semen quality in transgender women at the time of fertility preservation. STUDY DESIGN: In this cohort study, transgender women were included between May 2018 and September 2020, at the time of fertility counseling, before the start of hormonal treatment. Data were collected on demographics, lifestyle factors, medical history, endocrine laboratory results, and semen parameters. Semen parameters were categorized using reference values for human semen of the World Health Organization and compared with semen quality in the general population. The odds ratios with 95% confidence intervals were calculated using multivariable logistic regression analysis to assess the impact of tucking, wearing tight undergarments, and a low ejaculation frequency on semen quality, correcting for potential confounders. RESULTS: Overall, 113 transgender women were included. Median semen parameters were significantly decreased than the general population. Crude logistic regression analyses showed an association between always wearing tight undergarments (odds ratio, 3.06; 95% confidence interval, 1.11-8.49) and extensive tucking (odds ratio, 6.09; 95% confidence interval, 1.54-24.01) on having a total motile sperm count of <5 million. Multivariable analyses showed that the association with tucking was independent of demographic factors, lifestyle factors, and medical history (odds ratio, 7.95; 95% confidence interval, 1.66-37.99). However, this was not the case for the association with always wearing tight undergarments (odds ratio, 2.89; 95% confidence interval, 0.95-8.82). Ejaculation frequency did not influence total motile sperm count. CONCLUSION: Behavioral factors, including wearing tight undergarments and extensive tucking, may contribute to the lower semen quality in transgender women. These results will enable optimization of fertility counseling on how to adjust lifestyle before pursuing semen cryopreservation.


Subject(s)
Transgender Persons , Transsexualism , Cohort Studies , Female , Humans , Infant, Newborn , Male , Semen , Semen Analysis , Sperm Count
12.
BJU Int ; 129(4): 491-497, 2022 04.
Article in English | MEDLINE | ID: mdl-34390620

ABSTRACT

OBJECTIVE: To assess the incidence of testicular cancer in trans women (male sex assigned at birth, female gender identity) using gender-affirming hormonal treatment. PATIENTS AND METHODS: Data of trans women starting hormonal treatment at our gender identity clinic between 1972 and 2017 were linked to the national pathology database to obtain testicular cancer diagnoses. The standardised incidence ratio (SIR) was calculated using the number of observed testicular cancer cases in our cohort and the number of expected cases based on age-specific Dutch incidence rates. Subgroup analyses were performed in testicular tissues sent for histopathological analysis at the time of bilateral orchidectomy, and when follow-up exceeded 5 years. RESULTS: The cohort consisted of 3026 trans women with a median follow-up time of 2.3 interquartile range (IQR) (1.6-3.7) years. Two testicular cancer cases were identified whilst 2.4 cases were expected (SIR 0.8, 95% confidence interval 0.1-2.8). In addition, one testicular cancer case was encountered in an orchidectomy specimen (0.1%). In the 523 trans women with a follow-up time of >5 years (median [IQR] 8.9 [6.4-13.9] years), no testicular cancer was observed. CONCLUSION: Testicular cancer risk in trans women is similar to the risk in cis men. The testicular cancer cases occurred within the first 5 years after commencing hormonal treatment, and the percentage of cases encountered at the time of bilateral orchidectomy was low. As no testicular cancer was observed in trans women with a long follow-up period, long-term hormonal treatment does not seem to increase testicular cancer risk.


Subject(s)
Gender Identity , Testicular Neoplasms , Cohort Studies , Female , Humans , Incidence , Infant, Newborn , Male , Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms/epidemiology
13.
Sex Med ; 9(5): 100415, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34348219

ABSTRACT

INTRODUCTION: Genital gender affirming surgery (gGAS) is usually the final stage in the medical transition for transgender men and consists of creating a neophallus and neo-scrotum, with or without urethral lengthening(UL). To reduce the complication risks of UL, a mandatory colpectomy is performed prior to UL. Colpectomy is considered a complex surgery, which may lead to various perioperative complications. There are few long-term complications reported. AIM: To describe the clinical presentation and management of 3 consecutive transgender men presenting with a perineal cyst following gGAS. METHODS: After obtaining informed consent all clinical data was collected, including medical history, current symptoms, imaging, as well as surgery and histological outcomes. Furthermore, a literature search was performed. MAIN OUTCOME MEASURE: To hypothesize the aetiology of the perineal cyst based on current published literature. RESULTS: Three otherwise healthy transgender men, ages 26-46 with a similar medical history, presented with a perineal cyst several months or years following colpectomy and gGAS with UL. All patients underwent surgery to remove the cyst. Several theories regarding aetiology of this perineal cyst are discussed in this report. CONCLUSION: There remain several gaps in our knowledge regarding the aetiology and management of this perineal cyst. Therefore, further research is necessary. Asseler JD, Ronkes BL, Groenman FA, et al. Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview. J Sex Med 2021;9:100415.

14.
J Assist Reprod Genet ; 38(6): 1571-1588, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33725274

ABSTRACT

PURPOSE: Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? METHODS: Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 µM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. RESULTS: Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 µM GSK1070916 and the control. CONCLUSION: Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement.


Subject(s)
Aurora Kinase B/genetics , Aurora Kinase C/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myeloid, Acute/genetics , Apoptosis/drug effects , Aza Compounds/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cryopreservation , Female , Humans , Indoles/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Mitosis/drug effects , Mitosis/genetics , Neoplasm Metastasis , Ovarian Follicle/drug effects , Ovarian Follicle/growth & development , Signal Transduction/drug effects , Transplantation, Autologous/standards
15.
Int J Transgend Health ; 21(2): 138-146, 2020.
Article in English | MEDLINE | ID: mdl-33015665

ABSTRACT

Background: Masculinizing mastectomy is the most requested gender affirming surgery (GAS) in trans men, followed by genital GAS. Mastectomy and total laparoscopic hysterectomy, with or without bilateral salpingo-oophorectomy (TLH ± BSO), can both be performed in one single operation session. However, data on complication rates of the combined procedure is scarce and no consensus exists on the preferred order of procedures. Aims: To compare safety outcomes between mastectomy performed in a single procedure with those when performed in a combined procedure and assess whether the order of procedures matters when they are combined. Methods: A retrospective chart review was performed of trans men who underwent masculinizing mastectomy with or without TLH ± BSO in a combined session. The effects of the surgical procedure on complication and reoperation rate of the chest were assessed using logistic regression. Results: In total, 480 trans men were included in the study. Of these, 212 patients underwent the combined procedure. The gynecological procedure was performed first in 152 (71.7%) patients. In the total sample, postoperative hematoma of the chest occurred in 11.3%; 16% in the combined versus 7.5% in the single mastectomy group (p = 0.001). Reoperations due to hematoma of the chest were performed in 7.5% of all patients; 10.8% in the combined versus 4.9% in the single mastectomy group (p = 0.017). The order of procedures in the combined group had no significant effect on postoperative hematoma of the chest (p = 0.856), and reoperations (p = 0.689). Conclusion: Combining masculinizing mastectomy with TLH ± BSO in one session was associated with significantly more hematoma and reoperations compared with separately performing mastectomy. This increased risk of complications after a combined procedure should be considered when deciding on surgical options. The order of procedures in a combined procedure did not have an effect on safety outcomes.

16.
J Clin Endocrinol Metab ; 105(9)2020 09 01.
Article in English | MEDLINE | ID: mdl-32594155

ABSTRACT

CONTEXT: Trans women (male sex assigned at birth, female gender identity) mostly use antiandrogens combined with estrogens and can subsequently undergo vaginoplasty including orchiectomy. Because the prostate remains in situ after this procedure, trans women are still at risk for prostate cancer. OBJECTIVE: To assess the incidence of prostate cancer in trans women using hormone treatment. The incidence of prostate cancer in trans women using hormone treatment. DESIGN: In this nationwide retrospective cohort study, data of participants were linked to the Dutch national pathology database and to Statistics Netherlands to obtain data on prostate cancer diagnosis and mortality. SETTING: Gender identity clinic. PARTICIPANTS: Trans women who visited our clinic between 1972 and 2016 and received hormone treatment were included. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) were calculated using the number of observed prostate cancer cases in our cohort and the number of expected cases based on age-specific incidence numbers from the Netherlands Comprehensive Cancer Organization. RESULTS: The study population consisted of 2281 trans women with a median follow-up time of 14 years (interquartile range 7-24), and a total follow-up time of 37 117 years. Six prostate cancer cases were identified after a median 17 years of hormone treatment. This resulted in a lower prostate cancer risk in trans women than in Dutch reference males (SIR 0.20, 95% confidence interval 0.08-0.42). CONCLUSIONS: Trans women receiving androgen deprivation therapy and estrogens have a substantially lower risk for prostate cancer than the general male population. Our results support the hypothesis that androgen deprivation has a preventive effect on the initiation and development of prostate cancer.


Subject(s)
Androgen Antagonists/therapeutic use , Prostatic Neoplasms/epidemiology , Transsexualism/drug therapy , Transsexualism/epidemiology , Adult , Cohort Studies , Female , Follow-Up Studies , Gender Dysphoria/drug therapy , Gender Dysphoria/epidemiology , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology , Retrospective Studies , Risk Factors , Sex Reassignment Procedures , Young Adult
17.
J Sex Med ; 16(6): 924-933, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31036523

ABSTRACT

BACKGROUND: Colpectomy, removal of the vaginal epithelium, may be performed in transgender men because of a disturbed male self-image, to reduce vaginal discharge, or to reduce the risk of fistula formation at the urethral-neourethral junction in future phalloplasty or metaidoioplasty. AIM: To demonstrate that vaginal colpectomy in transgender men, either alone or in combination with, for example, laparoscopic hysterectomy, metaidoioplasty, scrotoplasty, or urethroplasty, is a feasible procedure. METHODS: This single-center retrospective cohort study included 143 transgender men who underwent vaginal colpectomy between January 2006 and April 2018. Surgical details and clinical outcomes were collected from all patients. OUTCOMES: The primary outcome was the number of perioperative and postoperative complications, including intraoperative blood loss. Secondary outcomes were operating time, change in hemoglobin level, and duration of hospital stay. RESULTS: In 109 patients (76%), the procedure consisted of colpectomy only, whereas in 34 patients (23%), colpectomy was combined with other procedures. In the whole group (combined procedures included), the median blood loss was 300 mL (interquartile range [IQR] = 250 mL), the mean operating time was 132 ± 62 minutes, and the mean duration of hospital admission was 3.6 ± 1.9 days. In the colpectomy-only group, the median blood loss was 300 mL (IQR = 250 mL), mean operating time was 112 ± 40 minutes, and mean duration of hospital admission was 3.2 ± 1.5 days. For the total group, 15 patients (10%) experienced a major perioperative complication (ie, bowel injury, ureter injury, urethra injury, bladder injury, hemorrhage requiring transfusion and/or intervention and conversion to laparoscopy), and 1 patient (0.7%) had a minor perioperative complication (hemorrhage). Major postoperative complications (hemorrhage, hematoma, fistula, wound infection and prolonged pain complaints) were reported in 17 patients (12%), and minor postoperative complications (urinary tract infection, urinary retention, hemorrhage, and hematoma) occurred in 50 patients (35%). CLINICAL IMPLICATIONS: This study provides a detailed description of our technique and comprehensive reporting on perioperative and postoperative complications and reintervention rate. STRENGTHS & LIMITATIONS: Study strengths include the large number of patients included and the detailed reporting on the complications of vaginal colpectomy. The main limitation is the retrospective design, which can cause data to go missing during extraction and is prone to bias. CONCLUSION: Vaginal colpectomy is a procedure with a high complication rate, but its advantages seem to outweigh its disadvantages. In all but 1 case, no long-term sequelae were reported. However, the high complication rate and reintervention rate should be discussed with patients who are considering undergoing this procedure. Nikkels C, van Trotsenburg M, Huirne J, et al. Vaginal Colpectomy in Transgender Men: A Retrospective Cohort Study on Surgical Procedure and Outcomes. J Sex Med 2019;16:924-933.


Subject(s)
Transsexualism/surgery , Vagina/surgery , Adult , Blood Loss, Surgical , Feasibility Studies , Female , Humans , Hysterectomy/methods , Intraoperative Complications/etiology , Laparoscopy/methods , Length of Stay/statistics & numerical data , Male , Middle Aged , Operative Time , Postoperative Cognitive Complications , Postoperative Complications/etiology , Retrospective Studies , Sex Reassignment Procedures/methods , Transgender Persons , Urethra/injuries , Urinary Retention/etiology , Urinary Tract Infections/etiology
18.
Reprod Biomed Online ; 38(6): 999-1009, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30954431

ABSTRACT

RESEARCH QUESTION: Can reflectance confocal microscopy (RCM) be used to determine follicle density in human ovarian cortex fragments that are intended for fertility restoration? DESIGN: RCM was used on living cortex tissue fragments derived from five bovine ovaries and 13 human ovaries. All tissue fragments were cryopreserved and thawed before RCM analysis. Follicle numbers and distribution were determined by RCM and histology. Before and after RCM, general tissue viability and follicle integrity were assessed by a glucose uptake assay and neutral red staining, respectively. RESULTS: RCM can detect all stages of follicle development in living ovarian tissue to a maximum depth of 250 µm. In bovine tissue, all follicles were located within this 0-250 µm range. In human ovarian tissue, follicles were also present below the 250 µm RCM threshold, implying that only a percentage of the total number of follicles could be detected with RCM. The percentage of follicles detected by RCM appeared to be age dependent. The RCM procedure did not affect the glucose uptake by the tissue, whereas neutral red staining indicated a high level of follicle survival. CONCLUSION: In this proof of concept study, we have shown that RCM is a promising technique to determine the density of follicles ex vivo in living human ovarian cortex fragments, apparently without compromising the vitality of the tissue. Safety studies and further optimization of the RCM technique with a focus on increasing the penetration depth are required before clinical use of RCM.


Subject(s)
Infertility, Female/therapy , Microscopy, Confocal , Ovarian Follicle/pathology , Ovary/diagnostic imaging , Ovary/transplantation , Transplantation, Autologous/methods , Adolescent , Adult , Animals , Blood Glucose/analysis , Cattle , Child , Child, Preschool , Cryopreservation/methods , Equipment Design , Female , Fertility Preservation/methods , Humans , Neutral Red/chemistry , Oocytes , Ovary/pathology , Tissue Culture Techniques , Young Adult
19.
J Sex Med ; 15(7): 1041-1048, 2018 07.
Article in English | MEDLINE | ID: mdl-29861358

ABSTRACT

BACKGROUND: As genital gender-affirming surgery (GAS) is a demanding and life-changing intervention, transmen should be able to make choices about the surgical treatment based on outcomes that are most important to them, while taking into consideration the concomitant risks involved. AIM: Develop a decision aid (DA) for genital surgery in transmen (DA-GST) that can assist both transmen and health care professionals (HCPs) in making a well-informed decision about the surgical treatment. METHODS: A qualitative focus group study was performed. 5 Focus groups were organized with both HCPs and transmen. These were led by an independent professional moderator. Data collected during these focus groups were analyzed to provide content for the DA. OUTCOMES: To develop content for a DA-GST. RESULTS: Data collected during the focus groups related to the treatment options, information deemed relevant by transmen, and the arguments for or against each treatment option. Collected items were divided into the following themes: outcome, quality of life, environment, sexuality, and beliefs. CLINICAL IMPLICATIONS: The tool will be useful in assisting both transmen and HCPs in the shared decision-making process regarding genital GAS by exploring which domains are most relevant for each specific individual. STRENGTHS & LIMITATIONS: This DA was developed according to an iterative participatory design approach to fit the needs of both transmen and HCPs. Issues that transmen find important and relevant pertaining to genital GAS were translated into arguments that were incorporated in the DA-GST. The study is limited by the group that had participated. Not all arguments for or against specific surgical options may be covered by the DA-GST. CONCLUSION: An online DA was developed to support transmen with their decision-making process concerning all surgical options for removal of reproductive organs and genital GAS. Özer M, Pigot GL, Bouman M-B, et al. Development of a Decision Aid for Genital Gender-Affirming Surgery in Transmen. J Sex Med 2018;15:1041-1048.


Subject(s)
Decision Support Techniques , Sex Reassignment Procedures/psychology , Transgender Persons/psychology , Decision Making, Shared , Female , Focus Groups , Humans , Male , Qualitative Research , Quality of Life , Reproducibility of Results , Risk Assessment , Risk Factors
20.
Article in English | MEDLINE | ID: mdl-26125101

ABSTRACT

OBJECTIVE: To study the impact on health-related quality of life (HRQoL) of treatment with systemic methotrexate (MTX) or expectant management in women with ectopic pregnancy or pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations. STUDY DESIGN: HRQoL was assessed alongside a randomized clinical trial (RCT) with the use of standard self-administered psychometric measure questionnaires. PATIENTS AND SETTING: All women who participated in the multicenter RCT comparing treatment with systemic MTX to expectant management in women with ectopic pregnancy or persisting PUL were eligible for the HRQoL measurements. MAIN OUTCOME MEASURE: HRQoL measures of three standardized questionnaires (SF-36, RSCL, HADS). RESULTS: Data were available for 64 of 73 women (78%) randomized in the RCT. We found no difference in HRQoL between the two treatment groups. The need for additional treatment, i.e. additional MTX injections or surgical intervention, had no impact on HRQoL. CONCLUSION: Women treated with MTX or expectant management for an ectopic pregnancy or persisting PUL have comparable quality of life.


Subject(s)
Abortifacient Agents, Nonsteroidal/therapeutic use , Health Status , Methotrexate/therapeutic use , Pregnancy, Ectopic/psychology , Pregnancy, Ectopic/therapy , Quality of Life , Watchful Waiting , Abortion, Therapeutic , Adult , Chorionic Gonadotropin/blood , Female , Humans , Pregnancy , Pregnancy, Ectopic/drug therapy , Surveys and Questionnaires
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