0000000000022399
AUTHOR
Juan A. Garcia-velasco
Impact of chronic endometritis in infertility: a SWOT analysis
Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chroni…
Plasma levels of soluble vascular endothelial growth factor receptor-1 may determine the onset of early and late ovarian hyperstimulation syndrome
BACKGROUND Ovarian hyperstimulation syndrome (OHSS) is a life-threatening condition associated with ovarian stimulation. Its pathophysiology is unknown and its treatment continues to be empirical. Early (E)- and late (L)-OHSS occur in women at risk, though not in all cases. Vascular endothelial growth factor (VEGF) is related to increased vascular permeability in OHSS. We analysed the dynamics of the VEGF system in E- and L-OHSS. METHODS A prospective cohort of women undergoing IVF-ICSI treatment were divided into groups. E-OHSS: Nonpregnant patients classified as women not at risk (group 1) (n = 11) and patients at risk who did not (group 2) (n = 18) and did (group 3) (n = 8) develop sever…
Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome
BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) typically occurs when ovaries are primed with FSH/ LH and subsequently exposed to hCG. The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). METHODS: A search of the literature was carried out using PubMed and the authors’ files. RESULTS: In rodents and humans, the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases during ovarian stimulation. With the administration of hCG, the expression of each rises to a maximum. Expression of VEGF/VEGFR-2 mRNAs correlates with enhanced VP, with both peaking 48 h following an injection of hCG. Imm…
Prevention of OHSS: Current strategies and new insights
Abstract Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition that affects young healthy patients. Many strategies have been proposed to prevent this syndrome. However, to avoid OHSS without compromising on IVF outcome is still a challenge. The most important action is to identify patients at risk even before ovarian stimulation is initiated and to give them special attention. Coasting is the most popular method to avoid/minimize OHSS. Cycle cancellation, cryopreservation, GnRH antagonists, GnRH agonists, i.v. albumin are other strategies that can provide some kind of benefit but do not completely avoid both early and late forms of OHSS and/or…
Type of culture media does not affect embryo kinetics: a time-lapse analysis of sibling oocytes
Are the morphokinetics of growing embryos affected by the type of culture media utilized?Morphokinetic parameters used for embryo selection are not affected between the two different concept culture media analyzed.Studies on the effect of culture media on human embryos have focused on evaluating different in-house and commercially available media as well as comparing outcomes among different commercial media. Nonetheless, the evaluation of embryo development in these studies was based on static observations and very little is known from a dynamic point of view.Prospective cohort study, October 2010 and April 2011.University-affiliated infertility center. Patients undergoing egg donation (n …
Oocyte donation outcome after oncological treatment in cancer survivors.
Objective To study reproductive outcome in patients cured of cancer who required oocyte donation (OD) owing to iatrogenic ovarian dysfunction. Design Multicenter, unmatched, retrospective cohorts study. Setting Private, university-affiliated group of clinics. Patient(s) Women treated and cured of cancer (n = 142) who underwent 333 cycles of OD (exposed group) and women without a previous cancer diagnosis (n = 17,844) who underwent 29,778 cycles of OD (unexposed cohort) between January 2000 and January 2012. Intervention(s) Retrospective chart review. Main Outcome Measure(s) Pregnancy, implantation, miscarriage, and ongoing pregnancy rates. Result(s) There were no differences in terms of pre…
Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study
Objective To compare the efficacy of oocyte vitrification (OV) with that of ovarian cortex cryopreservation and transplantation (OCT) in women undergoing gonadotoxic treatments. Design Prospective observational cohort study. Setting Not applicable. Patient(s) Candidates for chemo-/radiotherapy who joined our fertility preservation (FP) program were included in this study between 2005 and 2015. One cohort included 1,024 patients undergoing OV; the other cohort included 800 patients undergoing OCT. Intervention(s) OV using the cryotop device and OCT using a slow freezing protocol. Main Outcome Measure(s) Live-birth rate (LBR) and clinical pregnancy rate (CPR). Result(s) Basal antimullerian ho…
A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.
Abstract Research question Does clinical performance of personalized embryo transfer (PET) guided by endometrial receptivity analysis (ERA) differ from frozen embryo transfer (FET) or fresh embryo transfer in infertile patients undergoing IVF? Design Multicentre, open-label randomized controlled trial; 458 patients aged 37 years or younger undergoing IVF with blastocyst transfer at first appointment were randomized to PET guided by ERA, FET or fresh embryo transfer in 16 reproductive clinics. Results Clinical outcomes by intention-to-treat analysis were comparable, but cumulative pregnancy rate was significantly higher in the PET (93.6%) compared with FET (79.7%) (P = 0.0005) and fresh embr…
Serum interleukin-6 levels are elevated in women with minimal-mild endometriosis.
BACKGROUND: There is a need for a reliable marker of endometriosis, especially in early stages of peritoneal disease during which imaging is not effective. The use of serum interleukin (IL)-6 as a marker is controversial. To readdress the matter, patients undergoing laparoscopy were prospectively evaluated for serum IL-6 levels. MATERIALS AND METHODS: A total of 119 women 31 years old who underwent laparoscopy were divided into groups: control patients (n = 38) with no pathologic findings; endometriosis sufferers (n = 47) with minimal-mild (MM, n = 11) or moderate-severe (MS, n = 36) endometriosis; uterine myomas (n = 13) and benign ovarian pathologies (n = 21). Blood was drawn on cycles da…
Female obesity increases the risk of miscarriage of euploid embryos.
Objective To determine whether female body mass index (BMI) is associated with an increased risk of miscarriage after euploid embryo transfer. Design A retrospective, observational, multicenter cohort study. Setting University-affiliated in vitro fertilization center. Patient(s) In this study, 3,480 cycles of in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) in the blastocyst stage and euploid embryo transfer were divided into four groups according to patient BMI. Intervention(s) In vitro fertilization with PGT-A. Main Outcome Measure(s) The primary outcome was the miscarriage rate, which included both biochemical and clinical miscarriages. Secondary outcome…
Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study.
Abstract Objective To evaluate the reproductive and neonatal outcome of blastocyst transfer after coculture with human endometrial epithelial cells in IVF and oocyte donation. Design Retrospective study. Setting Private assisted reproductive center. Patient(s) Two hundred sixty women undergoing IVF and 469 oocyte recipients. Intervention(s) IVF or intracytoplasmic sperm injection (ICSI) and transfer of at least one blastocyst after coculture with human endometrial epithelial cells. Main outcome measure(s) Blastocyst formation rate, implantation and pregnancy rates, neonatal outcome, and congenital birth defects. Results Among patients who had transfer with their own oocytes, 1,193 of 2,349 …
Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis
Survival of newly implanted retrograde-shed endometrial tissue during menstruation in an ectopic location requires an adequate blood supply. This suggests that angiogenesis is a prerequisite for the development of endometriosis and that its inhibition may be a target for preventing development. Previous studies have shown that vascular endothelial growth factor (VEGF), a heparin-binding glycoprotein, has an essential role in angiogenesis. The main regulatory factor for angiogenesis appears to be binding of VEGF to its type-2 receptor (VEGFR-2). Cabergoline (Cb2) and other dopamine agonists promote endocytosis of the VEGF receptor-2 (VEGFR-2) in endothelial cells, thereby preventing VEGF-VEG…
Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors
Objective To analyze the reproductive outcome of recipients of donated ova according to their body mass index (BMI). Design Twelve-year retrospective cohort analysis. Setting Fertility clinics. Patient(s) 9,587 first cycles of ovum donation with ova from normoweight donors. Intervention(s) Recipients divided according to their BMI to analyze IVF laboratory and outcome parameters: lean with BMI 2 (n = 1,458; 15.2%); normoweight with BMI 20–24.9 kg/m 2 (n = 5,706; 59.5%), overweight with BMI 25–29.9 kg/m 2 (n = 1,770; 18.5%), and obese with BMI ≥30 kg/m 2 (n = 653; 6.8%). Main Outcome Measure(s) Implantation, biochemical and clinical pregnancy, miscarriage, and live-birth rates. Result(s) In …
The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis
Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the pot…
Sperm cryopreservation in oncological patients: a 14-year follow-up study.
Objective Oncologic treatments can destroy spermatogenic dividing cells and cause azoospermia which could be irreversible. Sperm banking is the best option to preserve male fertility after these treatments. It is easy, inexpensive, and safe. To date, few clinical data are available about large series of cancer patients. Our objective was to determine the usefulness of these preventive sperm freezing protocols. Design Prospective study. Setting University-affiliated private fertility center. Patient(s) One hundred eighty-six cancer patients who banked sperm samples at our center before surgery or chemo- or radiotherapy treatments from 1991 to 2004. Intervention(s) Conjugal status, age, type …
Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis
Objective To study the differences in the cleavage time between chromosomally normal and abnormal embryos and to elaborate an algorithm to increase the probability of noninvasively selecting chromosomally normal embryos. Design Retrospective cohort study. Setting University-affiliated infertility center. Patient(s) Preimplantation genetic screening patients (n = 125; n=77 with ET), including cases of repeated implantation failure or recurrent miscarriage. A total of 504 embryos were analyzed. Intervention(s) Embryo culture within a time-lapse system. Main Outcome Measure(s) Kinetic variables included the time to 2 (t2), 3 (t3), 4 (t4), and 5 (t5) cells as well as the length of the second (c…
Physiology and Pathology of Ovarian Hyperstimulation Syndrome
Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle-stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). With the administration of hCG, the expression vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. These findings suggest that the syndrome can be prevented…
The impact of using the combined oral contraceptive pill for cycle scheduling on gene expression related to endometrial receptivity.
STUDY QUESTION: Does the combined oral contraceptive pill (COCP) change endometrial gene expression when used for cycle programming? SUMMARY ANSWER: COCP used for scheduling purposes does not have a significant impact on endometrial gene expression related to endometrial receptivity. WHAT IS KNOWN ALREADY: Controversy exists around COCP pretreatment for IVF cycle programming as some authors claim that it might be detrimental to the live birth rate. Microarray technology applied to the study of tissue gene expression has previously revealed the behavior of genes related to endometrial receptivity under different conditions. STUDY DESIGN SIZE AND DURATION: Proof-of-concept study of 10 young h…
Is endometrial receptivity transcriptomics affected in women with endometriosis? A pilot study
Endometrial receptivity is still questioned today in women with endometriosis. The aim of this study was to assess the endometrial receptivity gene signature in patients with different stages of endometriosis by investigating transcriptomic modifications of their endometrium using the endometrial receptivity array (ERA) test. A prospective, interventional multicentre pilot trial was designed and implemented in two university-affiliated infertility units from Belgium and Spain. Gene expression microarray was used to diagnose the receptivity status by quantifying the expression of 238 specific genes directly related to human endometrial receptivity. Unsupervised hierarchical clustering showed…
Ovarian stimulation does not influence the uterine immune environment in healthy infertile women.
Abstract Research question There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF. Design This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screenin…
High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study
Background The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response. Methods We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: 1.81 ng/ml (>p90). Ovarian …
Ovarian stimulation for oocyte vitrification does not modify disease-free survival and overall survival rates in patients with early breast cancer
Research question: Does ovarian stimulation for oocyte vitrification affect disease-free survival and overall survival rates in women with early breast cancer? Design: This cohort study included 259 patients with early breast cancer; 148 patients underwent ovarian stimulation, whereas 111 patients did not. Patients were treated between January 2008 and December 2016. To calculate the disease-free survival time and overall survival rate, the time of definitive surgery was defined as the starting point. The follow-up was conducted up to 5 years. Results: Exposed and non-exposed groups were comparable in tumour, node and metastases classification, Nottingham grade, hormonal receptor status, tu…
Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis
Research question: How does the number of oocytes used affect the cumulative live birth rate in endometriosis patients who had their oocytes vitrified for fertility preservation (FP)? Design: Retrospective observational study including data from 485 women with endometriosis who underwent FP from January 2007 to July 2018. Survival curves and Kaplan-Meier plots were used to analyse the cumulative live birth rate (CLBR) according to the number of vitrified oocytes used. Data were stratified according to age, stage of the disease and ovarian surgery prior to FP (operated vs. non-operated). Endometriosis curves were compared to plots developed using elective fertility preservation (EFP) patient…
Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial
Abstract Background Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate. Methods Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts)…