Explainable artificial intelligence to identify follicles that optimize clinical outcomes during assisted conception.

Infertility affects one-in-six couples, often necessitating in vitro fertilization treatment (IVF). IVF generates complex data, which can challenge the utilization of the full richness of data during decision-making, leading to reliance on simple 'rules-of-thumb'. Machine learning techniques are well-suited to analyzing complex data to provide data-driven recommendations to improve decision-making.

Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial.

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%.

SARS-Cov-2 viral and serological screening of staff in 31 European fertility units.

Study Question: What is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral presence and seroconversion in staff members in European fertility units prior to recommencement of clinical activity?

Summary Answer: A large proportion of fertility clinic staff remain susceptible to SARS-CoV-2 with no evidence of seroconversion, indicating that continued comprehensive risk mitigation strategies are essential.

What Is Known Already: In response to the coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, routine fertility treatment was temporarily stopped in several European countries. The SARS-CoV-2 prevalence and seroconversion in fertility clinic staff, who are at potentially lower risk than routine healthcare workers, are unknown.

Endocrine Requirements for Oocyte Maturation Following hCG, GnRH Agonist, and Kisspeptin During IVF Treatment.

Objective: The maturation of oocytes to acquire competence for fertilization is critical to the success of fertilization (IVF) treatment. It requires LH-like exposure, provided by either human chorionic gonadotropin (hCG), or gonadotropin releasing hormone agonist (GnRHa). More recently, the hypothalamic stimulator, kisspeptin, was used to mature oocytes.

Anti-Müllerian hormone (AMH) in the Diagnosis of Menstrual Disturbance Due to Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a leading cause of female subfertility worldwide, however due to the heterogeneity of the disorder, the criteria for diagnosis remains subject to conjecture. In the present study, we evaluate the utility of serum Anti-Müllerian hormone (AMH) in the diagnosis of menstrual disturbance due to PCOS. Menstrual cycle length, serum AMH, gonadotropin and sex-hormone levels, total antral follicle count (AFC), body mass index (BMI) and ovarian morphology on ultrasound were analyzed in a cohort of 187 non-obese women, aged 18-35 years, screened for participation in a clinical trial of fertility treatment between 2013 and 2016 at a tertiary reproductive endocrine center.

FSH Requirements for Follicle Growth During Controlled Ovarian Stimulation.

Ovarian follicle growth is a key step in the success of assisted reproductive treatment, but limited data exists to directly relate follicle growth to recombinant FSH (rFSH) dose. In this study, we aim to evaluate FSH requirements for follicular growth during controlled ovarian stimulation. Single center retrospective cohort study of 1,034 IVF cycles conducted between January 2012-January 2016 at Hammersmith Hospital IVF unit, London, UK.

Follicle Size on Day of Trigger Most Likely to Yield a Mature Oocyte.

Objective: To identify follicle sizes on the day of trigger most likely to yield a mature oocyte following hCG, GnRH agonist (GnRHa), or kisspeptin during IVF treatment.

Design: Retrospective analysis to determine the size of follicles on day of trigger contributing most to the number of mature oocytes retrieved using generalized linear regression and random forest models applied to data from IVF cycles (2014-2017) in which either hCG, GnRHa, or kisspeptin trigger was used.

Setting: HCG and GnRHa data were collected at My Duc Hospital, Ho Chi Minh City, Vietnam, and kisspeptin data were collected at Hammersmith Hospital, London, UK.

A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

Study Question: Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)?

Summary Answer: A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS.

What Is Known Already: Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS.

A first-in-human, randomized, controlled, subject- and reviewer-blinded multicenter study of Actamax™ Adhesion Barrier.

Purpose: Post-surgical adhesions remain a significant concern following abdominopelvic surgery. This study was to assess safety, manageability and explore preliminary efficacy of applying a degradable hydrogel adhesion barrier to areas of surgical trauma following gynecologic laparoscopic abdominopelvic surgery.

Methods: This first-in-human, prospective, randomized, multicenter, subject- and reviewer-blinded clinical study was conducted in 78 premenopausal women (18-46 years) wishing to maintain fertility and undergoing gynecologic laparoscopic abdominopelvic surgery with planned clinically indicated second-look laparoscopy (SLL) at 4-12 weeks.

GnRH agonist trigger with intensive luteal phase support vs. human chorionic gonadotropin trigger in high responders: an observational study reporting pregnancy outcomes and incidence of ovarian hyperstimulation syndrome.

A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had ≥18 follicles ≥11mm or serum oestradiol >18,000pmol/l on the day of trigger.

Rescue hCG to treat empty follicle syndrome after the use of a GnRH agonist as oocyte maturation trigger: First report on fresh embryo transfer and clinical pregnancy.

We present a case series and literature review on the use of rescue human chorionic gonadotropin (hCG) in cases of empty follicle syndrome (EFS) after a gonadotropin-releasing hormone agonist (GnRHa) trigger. EFS was diagnosed after failure to collect any oocytes from one ovary. In such cases, a single dose of hCG was administered and the oocyte retrieval was repeated 36 h later.

Predicting formation of adhesions after gynaecological surgery: development of a risk score.

Purpose: Risk factors for post-surgical adhesions following gynaecological surgery have been identified, but their relative importance has not been precisely determined. No practical tool exists to help gynaecological surgeons evaluate the risk of adhesions in their patients. The purpose of the study was to develop an Adhesion Risk Score to provide a simple tool that will enable gynaecological surgeons to routinely quantify the risk of post-surgical adhesions in individual patients.

Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy.

Context: In vitro fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication, ovarian hyperstimulation syndrome (OHSS).

Objective: This study aimed to investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.

Setting And Design: This was a phase 2, multi-dose, open-label, randomized clinical trial of 60 women at high risk of developing OHSS carried out during 2013-2014 at Hammersmith Hospital IVF unit, London, United Kingdom.

Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization.

Background: Patients with mutations that inactivate kisspeptin signaling are infertile. Kisspeptin-54, the major circulating isoform of kisspeptin in humans, potently stimulates reproductive hormone secretion in humans. Animal studies suggest that kisspeptin is involved in generation of the luteinizing hormone surge, which is required for ovulation; therefore, we hypothesized that kisspeptin-54 could be used to trigger egg maturation in women undergoing in vitro fertilization therapy.

Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

Context: Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development.

Objective: Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries.

Endocrinological insights into different in vitro fertilization treatment aspects.

The science of reproductive endocrinology/in vitro fertilization (IVF) has moved forward considerably since the first IVF baby was born in 1978. IVF was originally indicated for women with tubal factor infertility, but it has now become the treatment for couples with unexplained subfertility, male subfertility, cervical factor, failed ovulation induction, endometriosis or unilateral tubal pathology. IVF was initially performed with the single dominant ovarian follicle produced during a spontaneous menstrual cycle.

The current place of tubal surgery in the management of subfertility.

Treatment of tubal disease can be challenging and complex. It requires accurate assessment of the extent of disease and evaluation of all fertility parameters. Although traditionally treatment involved salpingectomy or IVF or a combination of the two, less invasive treatment options may prove beneficial.

Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure.

Infertility and recurrent pregnancy loss (RPL) are prevalent but distinct causes of reproductive failure that often remain unexplained despite extensive investigations. Analysis of midsecretory endometrial samples revealed that SGK1, a kinase involved in epithelial ion transport and cell survival, is upregulated in unexplained infertility, most prominently in the luminal epithelium, but downregulated in the endometrium of women suffering from RPL. To determine the functional importance of these observations, we first expressed a constitutively active SGK1 mutant in the luminal epithelium of the mouse uterus.

In vitro fertilisation with recombinant follicle stimulating hormone requires less IU usage compared with highly purified human menopausal gonadotrophin: results from a European retrospective observational chart review.

Background: Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH) and highly purified human menopausal gonadotrophin (hMG-HP) required per cycle of in vitro fertilisation (IVF); the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice.

Methods: This retrospective chart review of databases from four European countries investigated gonadotrophin usage, oocyte and embryo yield, and pregnancy outcomes in IVF cycles (± intra-cytoplasmic sperm injection) using rFSH or hMG-HP alone. Included patients met the National Institute for Health and Clinical Excellence (NICE) guideline criteria for IVF and received either rFSH or hMG-HP.

The poly(c)-binding protein-1 regulates expression of the androgen receptor.

The androgen receptor (AR) is a ligand-dependent transcription factor, expressed in male and female reproductive organs, and essential for normal reproduction in both sexes. The levels of AR are tightly controlled in androgen-responsive cells in which it plays a central role in the regulation of target gene expression. The AR is abundantly expressed in human endometrial stromal cells (HESCs), but levels decline markedly after differentiation into decidual cells in vivo and in primary cultures.

Congenital uterine anomalies and their impact on fertility.

Congenital uterine anomalies are not uncommon. Many are asymptomatic and have been associated with normal and adverse reproductive outcomes. The interference of these anomalies with a patient's fertility is an interesting but still debatable issue, and the proper management of infertile women with many forms of these anomalies remains controversial.