Human reproduction open最新文献

[This corrects the article DOI: 10.1093/hropen/hoaf009.].

Study question: Are recombinant FSH (rFSH) and hCG effective therapies for promoting testicular growth and spermatogenesis in male adolescents and young adults with gonadotropin deficiency?

Summary answer: Combined gonadotropin therapy is effective in inducing puberty and promoting spermatogenesis in male adolescents and young adults with gonadotropin deficiency and has the potential to improve adult outcomes relating to both fertility and quality of life.

What is known already: Deficiency of pituitary gonadotropins (LH and FSH) due to hypogonadotropic hypogonadism (HH) can result in poor testicular development, low testicular volumes, micropenis and cryptorchidism. Inadequate hormonal replacement can lead to long-term issues, including subfertility or infertility, and reduced quality of life. Exogenous testosterone for pubertal induction can elevate serum testosterone concentrations and induce virilization, but it does not promote testicular development nor induce spermatogenesis. Fertility and testes growth remain primary concerns for patients seeking treatment.

Study design size duration: We conducted a retrospective observational review of male adolescents and young adults with gonadotropin deficiency and seeking puberty replacement therapy at two large tertiary centre hospitals in London, UK, from 2010 to 2024.

Participants/materials setting methods: A total of 35 males, with diagnosis of congenital hypogonadotropic hypogonadism (CHH: n = 23; further subdivided into those with partial [pHH: n = 8] and those with complete gonadotropin deficiency [cHH: n = 15]), acquired HH (AHH: n = 4) or Kallmann syndrome (KS: n = 8), received combined gonadotropin therapy. We assessed testicular growth and semen quality post-treatment.

Main results and the role of chance: The majority of patients were referred for pubertal delay, alone or in combination with cryptorchidism, micropenis or microorchidism. Out of 35 patients, 22 (63%) had previously received testosterone, and the median age at gonadotropin treatment initiation was 15.8 years (range: 11.8-22.7). Semen analysis was obtained in 18 out of 19 patients who had received gonadotropin therapy for a median treatment duration of 21.1 months (range: 4.5-66.9) for rFSH and 19.5 months (range: 8.3-61.1) for hCG. The median sperm count on semen analysis was 8.9 × 10⁶/ml (range: 0.0-54.9). Significant increases were noted in testicular volume (median change after therapy: 10.5 ml [95% CI 9.5-13.6], P < 0.0001), testosterone (median increase: 25.7 nmol/l [95% CI 19.8-31.5], P < 0.0001) and inhibin B levels (67.7 pg/ml [95% CI 18.4-86.7], P = 0.0008).

Limitations reasons for caution: The relatively low representation of patients with acquired HH in our study emphasizes the need to extrapolate the findings with caution in thi

Study question: What are the outcomes of controlled ovarian stimulation (COS) in childhood cancer survivors (CCS) undergoing fertility preservation (FP) after cancer treatment?

Summary answer: CCS who have undergone chemotherapy often show poor outcomes with COS and may need multiple cycles to achieve an adequate number of oocytes for future pregnancy.

What is known already: Up to 65% of CCS experience infertility from gonadotoxic treatments. Although it is ideal to consider FP at diagnosis, age and oncological factors often limit this option. After recovery, pubescent survivors, especially those who could not preserve fertility earlier, may be offered oocyte cryopreservation.

Study design size duration: A retrospective study including 20 CCS who underwent COS for oocyte storage between 2015 and 2022.

Participants/materials setting methods: This study involved young CCS who had been previously treated with chemotherapy and were evaluated at an FP center in a tertiary medical center. CCS were encouraged to pursue endocrine surveillance after recovering from cancer and were offered oocyte storage in case diminished ovarian reserve was evident, as dictated by elevated basal FSH (>10 IU/l), decreased anti-Müllerian hormone (AMH; <25th percentile for age), or low antral follicle count (<7).

Main results and the role of chance: Mean age at cancer diagnosis was 13.24 ± 5.6 years. Seventeen patients (85%) had been treated with alkylating agents, with five receiving cumulative doses greater than 4000 mg/m². At the time of FP, a median of 4.25 years after cancer diagnosis, the mean age of patients was 20.6 ± 3.56 years. Mean Day 3 FSH levels were 9.26 ± 3.4 IU/l, and 12 patients had AMH levels below 1 ng/ml. The first stimulation cycle lasted 9.4 ± 2.1 days, with a mean gonadotropin dose of 3246 ± 1057 IU and a median peak estradiol (E2) level of 3733 pmol/ml (IQR 1424-6796). The median number of oocytes retrieved in the first stimulation cycle was 5.5, with a median of four mature oocytes. By the end of the FP process, which involved 1-7 cycles per patient, the median number of oocytes stored was 13.5 (IQR 3.5-18.5). Twelve patients managed to store more than 10 oocytes.

Limitations reasons for caution: The study is exploratory in its nature, limited by its small sample size and its retrospective design.

Wider implications of the findings: Oocyte storage is feasible yet limited in young CCS. Despite their young age at the time of FP, CCS who have undergone chemotherapy often show poor outcomes with COS. Ongoing reproductive monitoring after recovery is crucial to identify those who would benefit from FP following cancer treatment.

Study funding/competing interests: The Fertility Preservation Unit funds (Sheba Medical Center) were used to suppor

Study question: Are the risks of adverse perinatal outcomes in singletons born from medically assisted reproduction (MAR) mainly associated with underlying parental infertility, or are they primarily linked to the MAR treatments?

Summary answer: While MAR-conceived singletons have increased risks of preterm birth, admission to neonatal intensive care unit (NICU), and hospital admission in early life, these risks are mainly associated with the underlying parental infertility that led to the use of MAR technologies.

What is known already: Children born from MAR are at increased risk for some adverse perinatal and infant outcomes. However, to what extent this risk is associated with infertility or MAR treatment remains unclear. This knowledge gap arises from the challenge in disentangling the effects of infertility and MAR treatment, given that parental infertility necessitates the use of MAR treatment.

Study design size duration: This is a statewide longitudinally data-linked population-based cohort study conducted in New South Wales, Australia, involving all singleton infants born (liveborn or stillborn) between 2009 and 2017.

Participants/materials setting methods: We applied two comparisons to isolate the associations of infertility from its treatment: (i) MAR infants versus naturally conceived infants from fertile parents (NC-fertile), and (ii) MAR infants versus naturally conceived infants from parents who had a history of infertility (NC-infertile). The study cohort consisted of 824 639 singleton infants, of whom 27 796 (3.4%) were conceived through ART and 13 574 (1.6%) through ovulation induction/intrauterine insemination (OI/IUI), while 783 269 (95.0%) of the infants were naturally conceived (747 018 NC-fertile controls and 36 251 NC-infertile controls). We used the inverse probability of treatment weighting method to make MAR infants comparable with each of the two NC control groups. We then calculated the adjusted risk differences (aRDs) in these propensity score-weighted cohorts. In the subgroup analyses of different forms of ART treatment (ICSI vs IVF and fresh vs frozen embryo transfer), we reweighted the study cohort and compared these subgroups with the two NC control groups separately.

Main results and the role of chance: Singletons conceived through ART had a higher risk for preterm birth (aRD 25.7 per 1000 infants, 95% CI 21.3-30.0), admission to NICU (aRD 8.4 per 1000 infants, 95% CI 1.2-15.6), and hospital admission within 2 years of life (aRD 24.6 per 1000 infants, 95% CI 17.2-32.0) compared to NC-fertile controls. These risks were notably reduced when compared to NC-infertile controls (aRD 9.5 per 1000 infants, 95% CI 4.8-14.2 for preterm birth; -0.7 per 1000 infants, 95% CI -8.0 to 6.6 for NICU admission; and 10.6 per 1000 infants, 95% CI 2.5-18.7 for hospital admission within 2 years of life