Portraits by Rafa Jenn

Rafa Jenn portrait of the artist skull print

Portrait of the Artist…

Rafa Jenn skull print

Portrait of the Viewer…

These posters by artist Rafa Jenn are so sweet, no wonder they sold out—small runs too. The work in general is awesome, but these skull posters are subtle and soft and just have a powerful glow. The red one is especially sweet, a wonderful addition for those who managed to snag one, lucky!

[via supersonicelectronic]

 

Blood Concept

Blood concept perfume

Blood Concept is blood type bottled and sold as fragrances. Based out of Italy, the company states that “BLOOD CONCEPT is a private celebration of the vivid and fascinating liquid that flows in our veins. Because blood is actually the river of life.” The fragrances, A, B, AB, and O are all unisex and feature scents from leather to black cherries to cedar wood. I don’t know my blood type, but I am going to assume I am B because it has a patchouli base.

To read more about the perfume check out the site, bloodconcept.com (which is also kind of visually pleasing).

[via BuzzFeed]

Visiting the Stigmatics of South Tyrol on Good Friday via The Wellcome Library, Circa 1840



...In the 1840s there was a steady flow of foreign tourists and pilgrims to the idyllic valleys of [South Tyrol] ... solely to visit two women who were said to have received spontaneously bleeding wounds (stigmata) on their hands, feet, or head like those caused to Jesus Christ when he was nailed to the cross and forced to wear the crown of thorns. One of the two women was Maria Domenica Lazzari (sometimes spelled Lazzeri), and the other was Maria von Moehrl (also called Mörl). The former was known as L'Addolorata (the woman of pain), the latter as L'Estatica (the woman of ecstasy), for reasons which will become clear.

On this Good Friday -- the holiday commemorating Jesus Christ's death by crucification -- why not take a moment to consider the medio-religious condition of stigmata, ie. spontaneous bleeding (mostly found in the female persuasion) on the hands, feet, and/or head, mimicking the wounds caused to Jesus Christ when he was nailed to the cross and forced to wear the crown of thorns?

All of the above text and images are drawn from two recent fascinating posts on the Wellcome Library blog; To read the full articles, click here and here.

Happy Good Friday!

Images, top to bottom (please click images to view larger, more detailed versions):

  1. Maria Domenica Lazzari. Coloured engraving, ca 1840. Wellcome Library no. 260i
  2. Maria von Moehrl. Watercolour by L. Giuditti after L.G. de Ségur, 1846. Wellcome Library no. 708243i
  3. Maria Domenica Lazzari. Watercolour by L. Giuditti after L.G. de Ségur, 1846. Wellcome Library no. 708242i

Tonight and Tomorrow at Observatory: Extreme Taxidermy and Dubiously Sourced Bodies and Anatomical Learning!

Tonight and tomorrow night at Observatory; hope to see you there!

Kitten Tea Parties, Auto Icons, and Habitat Groups: A Brief History of Taxidermy
An Illustrated Lecture by Dr. Pat Morris, Royal Holloway, University of London

Date: TONIGHT! Thursday, April 21
Time: 8:00 PM
Admission: $5

Tonight, taxidermy scholar and collector Pat Morris will discuss the fascinating and sometimes bizarre history of taxidermy as explored in his new book A History of Taxidermy: Art, Science and Bad Taste. Along the way, Morris will discuss anthropomorphic taxidermy of the sort made famous by Victorian museologist and taxidermist Walter Potter, "extreme taxidermy" (ie. human taxidermy), and the role of taxidermy in the history of scientific display and popular culture. He will also detail the development of taxidermy as an art form, tracing its development from the stiff rudimentary mounts which characterized its beginnings to the artistic triumphs of the late 19th and early 20th Centuries.

Copies of his new book History of Taxidermy: Art, Science and Bad Taste will also be available for sale and signing.

Dr. Pat Morris is a retired staff member of Royal Holloway College (University of London), where he taught biology undergraduates and supervised research on mammal ecology. In that capacity he has published many books and scientific papers and featured regularly in radio and TV broadcasts. The history of taxidermy has been a lifelong hobby interest and he has published academic papers and several books on the subject. With his wife Mary he has travelled widely, including most of Europe and the USA, seeking interesting taxidermy specimens and stories. They live in England where their house is home to the largest collection and archive of historical taxidermy in Britain.


Ill-gotten Brains: The Grisly History of Sourcing Bodies for Anatomical Learning
An Illustrated Lecture with Megan Curran, Norris Medical Library, USC
Date: TOMORROW, Friday, April 22
Time: 8:00 PM
Admission: $5

The idea of donating your body to science is actually a very new concept. There wasn’t even a national law governing the process until the late 1960s. How, then, did medical illustrators, going back hundreds of years, acquire bodies to draw? Many bodies were “donated” alright, but the dead people didn’t know they were being so generous. Prisoners, the indigent, robbed graves, and even murders helped supply medical schools and doctors for centuries.

This wild history of sourcing human bodies spans from the dawn of modern anatomy in the Renaissance with Vesalius (and even artists like Da Vinci and Michelangelo), through the 19th century's institutionalized medical school body snatchings, and up to Nazi medicine and the controversy over plastinated bodies in exhibits like Body Worlds.

For tonight's lecture, join Megan Curran of USC's Norris Medical Library for fascinating accounts of how bodies were procured for the advance of science, often through less than ethical means, accompanied by images from USC's rare medical books.

Megan Curran is the Head of Metadata & Content Management for the Norris Medical Library of the University of Southern California in Los Angeles, CA. Megan manages the history of medicine and rare books collections at USC and has been working to promote that collection. Megan serves on the editorial board of the Journal of the Medical Library Association, and is on the board of the Archivists & Librarians in the History of the Health Sciences. Megan originally hails from Philadelphia and is a dyed-in-the-wool rare book nerd.

You can find out more about these events on the Observatory website by clicking here and here; You can get directions to Observatory--which is next door to the Morbid Anatomy Library (more on that here)--by clicking here. You can find out more about Observatory here, join our mailing list by clicking here, and join us on Facebook by clicking here.

Images: Top: The Auto-Icon of Jeremy Bentham. Mr. Bentham requested in his will that his body be preserved and stored in a wooden cabinet. It has been on display since 1850 at University College London. Photo by Joanna Ebenstein.
Bottom: Opera omnia anatomica & chirurgica, Andreas Vesalius

Italian Devil Automaton, 15th or 16th Century, From the Wunderkammer of Ludovico Settala


Automata were... theologically and culturally familiar, things with which one could be on easy terms. They were funny, sometimes bawdy, and they were everywhere... Mechanical devils were...rife. Poised in sacristies, they made horrible faces, howled and stuck out their tongues to instill fear in the hearts of sinners. The Satan-machines rolled their eyes and flailed their arms and wings; some even had moveable horns and crowns. A muscular, crank-operated devil with sharply pointed ears and wild eyes remains in residence at the Castello Sforzesco in Milan.
--Jessica Riskin, “Machines in the Garden.” Republics of Letters: A Journal for the Study of Knowledge, Politics, and the Arts 1, no. 2 (April 3, 2010)

In her article "Machines in the Garden," Jessica Riskin discusses the use of automatons for religious purposes. Some of my favorite examples include mechanical devils intended to frighten church visitors into obedience (as shown and quoted above); mechanical passion plays; and a mechanical Christ on the crucifix popular in the 15th Century, which was able

to bow down and lifte up it selfe, to shake and stirre the handes and feete, to nod the head, to rolle the eies, to wag the chaps, to bende the browes, ... and gathering a frowning, forward, and disdainful face, when it would pretend offence: and shewing a most milde, amiable, and smyling cheere and countenaunce, when it woulde seeme to be well pleased. --William Lambarde, A Perambulation of Kent: Conteining the Description, Hystorie, and Customes of that Shire. Written in the Yeere 1570. by William Lambarde of Lincolns Inne Gent

I highly encourage you to read this fascinating article in its entirety; you can do so by clicking here.

Images: Italian Automaton (The Devil), carved in wood, 15th and 16th centuries, from the Wunderkammer owned by Ludovico Settala. It could, in the words of the Cosmodromium Blog, "roll its eyes and move its tongue, emit a noise and spit smoke from the mouth." Images sourced here.

All images and ideas sourced from the Cosmodromium Blog; read whole post--and see additional images--by clicking here.

An investigation of the potential effect of vacuoles in human sperm on DNA damage using a chromosome assay and the TUNEL assay

BACKGROUND

The aims of this study were to establish whether individual differences exist in the frequency and size of vacuoles found in human sperm and to ascertain whether such vacuoles are involved in causing DNA damage.

METHODS

Morphologically normal sperm were obtained from 15 IVF and 2 ICSI patients and 3 fertile donors. (i) Sperm heads were analyzed for the presence of vacuoles under a 1000x differential interference contrast microscope. (ii) In three patients and two donor samples, structural chromosomal damage was evaluated in normal sperm containing large vacuoles and selected at 1000x magnification for injection into mouse oocytes. (iii) In 10 patients and two donor samples, confocal laser microscopy detected DNA damage in sperm-exhibiting large vacuoles and stained with an in situ cell death detection kit.

RESULTS

(i) Vacuoles were observed in almost all normal sperm from patient and donor ejaculates and were mainly located at the tip or middle area of the sperm heads. However, average incidence of normal sperm exhibiting large vacuoles was 4.6 and 4.2% in the patient and donor groups, respectively. (ii) Sperm chromosome assays did not reveal any differences in the incidence of structural chromosome aberrations between sperm exhibiting large vacuoles and those without them (9.1 versus 4.1%). (iii) No significant difference in frequency of TUNEL-positive cells was found between normal sperm with large vacuoles and those without them in the samples examined. Among 227 sperm exhibiting large vacuoles, only 7 cells were TUNEL positive.

CONCLUSION

The results showed that large vacuoles were not responsible for DNA damage, suggesting that intra-cytoplasmic injection of morphologically selected sperm may not be required for patients who produce high-quality semen.

Seminal plasma protects human spermatozoa and pathogenic yeasts from capture by dendritic cells

BACKGROUND

During the process of fertilization, human spermatozoa are confronted with phagocytic cells of the female reproductive tract. Part of this host mucosal barrier are immature dendritic cells (DCs), which play an important role in the defense of invading microbial pathogens. In the present study, we investigated the potential interaction of spermatozoa with DCs and raised the question of whether seminal plasma impacts the interaction of DCs with spermatozoa or pathogenic microbes.

METHODS AND RESULTS

Flow cytometry and microscopy detected a strong association between spermatozoa and human monocyte-derived DCs, which was partly mediated by the DC-specific adhesion receptor, DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Coincubation assays also showed that capture of spermatozoa by DCs was blocked in the presence of increasing concentrations of seminal plasma. This inhibitory effect of seminal plasma was accompanied by altered DC maturation, revealed by flow cytometry analysis of maturation-specific DC surface markers. Phalloidin-staining of the DC cytoskeleton further visualized an impact of seminal plasma on DC morphology. To elucidate the molecular nature of the inhibitory activity of seminal plasma on sperm–DC -association, binding assays were performed in the presence of individual seminal plasma components. This approach identified specific prostaglandins—in particular, PGEl, 19-OH-PGEl and PGE2, which are present in seminal plasma at high concentrations—as likely inhibitory factors. In contrast to glass beads, the yeast Candida albicans, a common commensal organism and frequent pathogen of the genital tract, was also found to be protected from capture by DCs in the presence of seminal plasma or the specific prostaglandins.

CONCLUSIONS

The immunomodulatory power of seminal plasma may help spermatozoa to circumvent the attack of DCs of the female reproductive tract, thereby supporting successful fertilization. At the same time, however, such protective effects of seminal plasma may also modulate DC action during host–pathogen interactions.

Prenatal and adult exposures to smoking are associated with adverse effects on reproductive hormones, semen quality, final height and body mass index

BACKGROUND

Exposure to tobacco smoking prenatally is a risk factor for reduced semen quality, but whether the exposure has adverse effects on reproductive hormones, pubertal development or adult BMI remain largely unexplored. The aim of this study was to investigate the associations between these factors while controlling for the effects of current smoking in young adulthood.

METHODS

This cross-sectional study (1996–2006) included 3486 Danish men (median age: 19 years), participating in a semen-quality study. Data were obtained from questionnaires, physical examinations, semen analyses and assessments of reproductive hormones. The main outcome measures were markers of pubertal onset, BMI, reproductive hormones and semen variables.

RESULTS

Maternal smoking during pregnancy was associated with earlier onset of puberty (e.g. early pubic hair development in 25.2 versus 18.9% of unexposed subjects), lower final adult height (median: 1.80 versus 1.82 cm), higher BMI (22.9 versus 22.4), smaller testicles (14.0 versus 14.5 ml), lower total sperm counts (119 versus 150 million), reduced spermatogenesis-related hormones (e.g. inhibin-B/FSH 66 versus 73 pg/mU) and higher calculated free testosterone (free-T, 2.38 versus 2.33 nmol/l). If not exposed prenatally, men's own smoking was associated with increased total testosterone but unchanged free-T. For smokers who had been exposed prenatally, total testosterone was increased but free-T was reduced (2.30 versus 2.38 nmol/l, P = 0.003) due to higher levels of sex hormone-binding globulin.

CONCLUSIONS

Prenatal exposure to tobacco may lead to faster pubertal development possibly caused by a higher free-T, and to higher adult BMI and impairment of testicular function. The findings may not be clinical relevant for the individual but are of public health importance, and add to the knowledge of effects of tobacco smoking.

No secular trend over the last decade in sperm counts among Swedish men from the general population

INTRODUCTION

Based on historical data, a decline in sperm counts during the years 1940–1990 has been suggested and aetiologically linked to a concomitant increase in the incidence of testicular cancer. This study, focusing on possible changes in sperm parameters among young Swedish men, during the past 10 years, was specifically designed in order to answer the question of whether there is a continuing decline in sperm counts.

METHODS

During the period 2008–2010, 295 young (17–20 years; median 18) men born and raised in Sweden were recruited at the age they were supposed to undergo medical examination prior to military service. The participants filled in questionnaires, underwent andrological examination and delivered an ejaculate. Their semen parameters were compared with those of a similar cohort of men (n = 216) recruited in the year 2000–2001.

RESULTS

No significant changes (means; 2000–2001 versus 2008–2010) in sperm concentration (78 x 106/ml versus 82 x 106/ml; P = 0.54), semen volume (3.1 ml versus 3.0 ml; P = 0.26) or total sperm counts (220 x 106 versus 250 x 106; P = 0.18) were found. The proportion of progressively motile spermatozoa also remained unchanged.

CONCLUSIONS

Between the years 2000 and 2010 we found no evidence of time-related deterioration of semen parameters among young Swedish men from the general population. This finding does not exclude that such a decrease may have taken place before year 2000. If the risk of testicular cancer is linked to the sperm counts, the increase in incidence of this malignancy should be levelling off in southern Sweden in the next 10–15 years.

Does cessation of progesterone supplementation during early pregnancy in patients treated with recFSH/GnRH antagonist affect ongoing pregnancy rates? A randomized controlled trial

BACKGROUND

The aim of this study was to assess whether the cessation of progesterone (P) supplementation during early pregnancy after GnRH antagonist cycles is not inferior to its continuation in terms of pregnancy rates beyond 12 weeks of gestation

METHODS

There were 200 patients, with a positive β-hCG test (followed by a doubling in β-hCG levels 48 h later) after a fixed recombinant FSH (recFSH)/GnRH antagonist protocol for IVF/ICSI and a Day-3 fresh embryo transfer (ET), participated in this randomized controlled study. All patients received luteal support, with 200 mg vaginal P being administered three times daily for 14 days, beginning on the day of ET until the second β-hCG test, 16 days post-ET. In the control group (n = 100) the administration of P was continued until 7 weeks of gestation. In the study group (n = 100), vaginal P was discontinued on the 16th day post-ET

RESULTS

The ongoing pregnancy rate beyond 12 weeks, the primary outcome measure, did not differ between the study and control groups (82 versus 73%, P = 0.175; difference 9%, 95% CI: –2.6 to 20.3). There were also no significant differences observed between the study and control group in terms of abortion before or after 7 weeks of gestation [(9 versus 12%, P = 0.645) and (8 versus 10%, P = 0.806), respectively]. The same was true for bleeding episodes (14 versus 19%, P = 0.446).

CONCLUSIONS

After recFSH/GnRH antagonist cycles, the withdrawal of P supplementation in early pregnancy, with normally increasing β-hCG levels on the 16th day post-ET, had no significant clinical impact in terms of ongoing pregnancy rates beyond 12 weeks.

Glial cell missing-1 mediates over-expression of tissue inhibitor of metalloproteinase-4 in severe pre-eclamptic placental villi

BACKGROUND

Severe pre-eclampsia (sPE) causes significant maternal morbidity and intrauterine growth restriction as a result of severe placental dysfunction. Defects in the formation of both extra-villous and villous trophoblast are characteristic of this disease. The outer syncytiotrophoblast layer covering the placental villi develops syncytial knots and focal necrosis while reduced invasion of the extra-villous trophoblast results in a reduced maternal blood supply and ischemia of the placental villi. The transcription factor glial cell missing-1 (GCM1) regulates formation of both types of trophoblast. GCM1 expression is reduced in placental villi of women with sPE but the functional downstream consequences of reduced GCM1 expression are unknown.

METHODS AND RESULTS

In floating first trimester villous explants we demonstrated increased mRNA (2.5-fold, n = 12) and protein level (9.8-fold) of tissue inhibitor of metalloproteinase-4 (TIMP4) following repression of GCM1 (70 ± 7%) by small interfering-RNA, using RT–PCR and western blot, respectively. Similar increases in TIMP4 mRNA (4.2-fold, n = 7, P< 0.001 versus control) and protein levels were found following gene silencing of GCM1 in BeWo cells (<90% knock down of protein). TIMP4 protein was increased in placenta from women with sPE (3.5 ± 0.4 pg/µg, n = 8), compared with preterm (1.7 ± 0.17 pg/µg, n = 9) and term controls (1.6 ± 0.16 pg/µg, n = 9; P< 0.01; quantified by enzyme-linked immunosorbent assay and visualized using immunohistochemistry) with reduced GCM1 expression, mostly in the pathologic syncytial knots.

CONCLUSIONS

TIMP4 is a downstream target of GCM1 that may link the consequences of reduced GCM-1-directed trophoblast differentiation to histologic and functional components of disordered placentation in sPE.

Cumulus cell gene expression predicts better cleavage-stage embryo or blastocyst development and pregnancy for ICSI patients

BACKGROUND

Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model.

METHODS

From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n= 25) or GnRH agonist and highly purified menotrophin (n= 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed.

RESULTS

Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P< 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of >70% and a specificity of >90%.

CONCLUSIONS

Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.

Dynamic distribution of NuMA and microtubules in human fetal fibroblasts, developing oocytes and somatic cell nuclear transferred embryos

BACKGROUND

The nuclear mitotic apparatus (NuMA) plays a central role in the assembly and maintenance of spindle poles. Somatic cell nuclear transfer (SCNT) studies on non-human primates have shown that meiotic spindle removal during enucleation causes depletion of NuMA and the minus-end-directed motor protein (HSET) from the ooplasm, and this in turn leads to failure of embryo development. To determine whether NuMA from somatic cells could compensate for NuMA loss during enucleation, the distribution of NuMA and microtubule organization were investigated in human fibroblasts, developing oocytes and SCNT embryos.

METHODS

Human fetal fibroblasts, oocytes at various maturation stages and human embryos reconstructed by different SCNT methods were analyzed for NuMA and α-tubulin using immunofluorescent confocal microscopy.

RESULTS

NuMA was detected in interphase nuclei of fibroblasts and oocytes. During mitosis and meiosis, NuMA relocated to the domain surrounding the two spindle poles. During the enucleation process, NuMA was removed along with the meiotic spindle. At 2 h after injection into a donor cell, transitory bipolar spindles were organized and NuMA was detected in the reformed poles. NuMA could be detected spreading uniformly across the nucleoplasm of one pseudo-pronucleus in SCNT embryos but was excluded from the nucleolus. Regardless of the method used for SCNT (enucleation-injection or injection-pronuclei enucleation), NuMA aggregated and relocated to the reformed spindle poles at metaphase of the first mitotic event. At interphase, NuMA relocated throughout the nucleus in developmentally arrested SCNT embryos.

CONCLUSIONS

Our results show that donor cell nuclei contain NuMA, which might contribute to the maintenance of spindle morphology in SCNT embryos. Normal spindle and NuMA expression were found in human SCNT embryos at different developmental stages.

Secondary follicle growth and oocyte maturation during encapsulated three-dimensional culture in rhesus monkeys: effects of gonadotrophins, oxygen and fetuin

BACKGROUND

An alginate-based matrix supports the three-dimensional (3D) architecture of non-human primate follicles and, in the presence of FSH, permits the in vitro development of pre-antral follicles to the small antral stage, including the production of ovarian steroids and paracrine factors. The current study investigated the ability of gonadotrophins, fetuin and oxygen (O2) to improve primate follicle growth and oocyte maturation in vitro.

METHODS

Macaque secondary follicles were isolated from the early follicular phase ovaries, encapsulated in a sodium alginate matrix and cultured individually for 40 days in supplemented medium. The effects of recombinant human (rh) FSH (15, 3 and 0.3 ng/ml for high, medium and low FSH, respectively), bovine fetuin (1 or 0 mg/ml) and O2 (5 or 20% v/v) were examined. Half of the follicles in each culture condition received rhLH on Day 30–40. Follicles that reached antral stage were treated with rh chorionic gonadotrophin for 34 h to initiate oocyte meiotic maturation. Media were analyzed for ovarian steroids and anti-müllerian hormone (AMH).

RESULTS

Improved culture conditions supported non-human primate, secondary follicle growth to the antral stage and, for the first time, promoted oocyte maturation to the MII stage. In the presence of fetuin at 5% O2, follicles had the highest survival rate if cultured with high or medium FSH, whereas follicles grew to larger diameters at Week 5 in low FSH. Oocyte health and maturation were promoted under 5% O2. High FSHstimulated steroid production by growing follicles, and steroidogenesis by follicles cultured with low FSH was promoted by LH. AMH biosynthesis was elevated with high compared with low FSH and for longer under 5% O2 than under 20% O2.

CONCLUSIONS

This encapsulated 3D culture model permits further studies on the endocrine and local factors that influence primate follicle growth and oocyte maturation, with relevance to enhancing fertility preservation options in women.

Impact of intraperitoneal pressure and duration of surgery on levels of tissue plasminogen activator and plasminogen activator inhibitor-1 mRNA in peritoneal tissues during laparoscopic surgery

BACKGROUND

Our objective was to evaluate the impact of intraperitoneal pressure (IPP) and duration of a CO2 pneumoperitoneum on the peritoneal fibrinolytic system during laparoscopic surgery.

METHODS

Human study: Patients undergoing laparoscopic surgery were divided into two groups: low (8 mmHg, n= 32) or standard (12 mmHg, n= 36) IPP. Normal peritoneum was collected from the parietal wall at the beginning of surgery and every 60 min thereafter. Mouse study: Mice were divided into three groups: low (2 mmHg) or high (8 mmHg) IPP or laparotomy. Peritoneal tissue was collected at 0, 4, 8, 24, 48 and 72 h, and 5 and 7 days after surgery. Real-time RT–PCR was performed in humans and mice to measure the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) mRNA in peritoneal tissues.

RESULTS

Human study: The tPA/PAI-1 mRNA ratio was significantly decreased in the 12 mmHg group at 1 h [P< 0.0001 versus matched initial peritoneal biopsies (MI)]. The tPA/PAI-1 mRNA ratio decreased in both groups at 2 h (P< .0.01 versus MI). Mouse study: The tPA/PAI-1 ratio was decreased at 0 h, and the difference was significant at 4 h in both the laparotomy (P< 0.001 versus controls, 0 h, 5 and 7 days) and high-IPP (P< 0.0001 versus 0, 48 and 72 h, 5 and 7 days) groups. No changes in tPA/PAI-1 ratio were observed in the low-IPP group.

CONCLUSIONS

A low IPP and shorter duration of surgery appear to minimally impact the fibrinolytic system during a CO2 pneumoperitoneum.

microRNAs expression in endometriosis and their relation to angiogenic factors

BACKGROUND

Endometriosis is a common, multifactorial disease in which angiogenesis may be involved in the growth of endometrium outside the uterus. microRNAs (miRNAs) are 21–22 nucleotide non-coding RNAs that regulate gene expression and play fundamental roles in biological processes. The objective of this study was to analyze several miRNAs related to angiogenesis and the angiogenic factors, vascular endothelial growth factor-A (VEGF-A) and thrombospondin-1 (TSP-1), in endometriotic lesions (ovarian endometrioma, peritoneal lesion and rectovaginal nodule) and eutopic endometrium from women with endometriosis.

METHODS

TaqMan real-time PCR was used to assess the expression of the miRNAs (miR-15b, -16, -17-5p, -20a, -21, -125a, -221 and -222), while VEGF-A and TSP-1 mRNA were assessed by real-time PCR, with SYBR Green I and VEGF-A and TSP-1 protein levels were quantified by ELISA. Included in the study were 58 women with endometriosis and 38 control women.

RESULTS

In paired samples, ovarian endometrioma showed significantly lower VEGF-A mRNA (P =0.02) and protein (P=0.002) expression than eutopic endometrium and higher expression of miR-125a (P=0.003) and miR-222 (P <0.001). However, ovarian endometrioma had significantly higher expression of the angiogenic inhibitor TSP-1 and lower expression of miR-17-5p than eutopic endometrium (P<0.001). Moreover, a significant inverse correlations between miR-222 and VEGF-A protein levels (–0.267, P=0.018) and between miR-17-5p and TSP-1 protein levels (–0.260, P=0.022) were observed. Peritoneal lesions showed a significant increase in VEGF-A in comparison with ovarian endometrioma (P<0.01).

CONCLUSIONS

Expression levels of miRNAs related to angiogenesis were different in eutopic endometrium from that observed in ovarian endometrioma. This could influence the expression of angiogenic factors and play a role in the pathogenesis of endometriosis.

Timing oocyte collection in GnRH agonists down-regulated IVF and ICSI cycles: a randomized clinical trial

BACKGROUND

The evidence underpinning the timing of an oocyte collection in IVF or ICSI is limited. The aim of this study was to assess the effect of the follicle diameter size of the dominant follicle on ongoing pregnancy rates.

METHODS

We conducted a randomized controlled trial, including women aged between 18 and 43 years who were scheduled for GnRH agonist down-regulated IVF/ICSI treatment in four assisted conception units. Women were randomized between timing oocyte collection when the leading follicle had a diameter of 22 mm or when the leading follicle had a diameter of 18 mm. The primary end-point was ongoing pregnancy, defined as a viable pregnancy at 12 weeks of gestation.

RESULTS

The trial had major problems with recruiting patients and after the planned 2 years of recruiting only half of the aimed 400 inclusions were obtained. We allocated 97 women to the 22-mm group and 93 women to the 18-mm group. In the 22-mm group more women reached an ongoing pregnancy (37 of 97 women, 38%) compared with the 18-mm group (22 of 93 women, 24%) resulting in a relative risk of 1.6 [95% confidence interval (CI): 1.03–2.5]. In a logistic regression analysis, the timing of oocyte collection, adjusted for female age, IVF/ICSI and centre, was still associated with ongoing pregnancy, although the association was no longer statistically significant (OR: 2.0; 95% CI: 0.96–4.2)

CONCLUSIONS

This study suggests that delaying the timing of oocyte collection in IVF or ICSI results in better ongoing pregnancy rates, however, larger studies have to be performed to prove or refute these findings.

Trial registration: ISRCTN24724622.

The addition of GnRH antagonists in intrauterine insemination cycles with mild ovarian hyperstimulation does not increase live birth rates–a randomized, double-blinded, placebo-controlled trial

BACKGROUND

This multicenter, double-blinded RCT investigated the efficacy of GnRH antagonists in cycles with mild ovarian hyperstimulation (MOH) followed by IUI in subfertile women.

METHODS

Couples diagnosed with unexplained, male factor subfertility or associated with the presence of minimal or mild endometriosis were randomized with a computer-generated list of numbers by a third party in a double-blinded setting to receive either a GnRH antagonists or a placebo in 12 institutional or academic hospitals. All women were treated with recombinant FSH in a low-dose step-up regimen starting on Day 2–4 of the cycle. A GnRH  antagonist was added when one or more follicles of 14 mm diameter or more were visualized. When at least one follicle reached a size of ≥18 mm, ovulation was induced by hCG injection. A single IUI was performed 38–40 h later. Couples were offered a maximum of three consecutive cycles. The primary outcome of the trial was live births. Secondary outcomes were pregnancy rates, multiple pregnancy rates, miscarriages and ovarian hyperstimulation syndrome rate.

RESULTS

A total of 233 couples were included from January 2006 to February 2009, starting 572 treatment cycles. Live birth rates were not significantly different between the group treated with GnRH antagonist (8.4%; 23/275) and the placebo group (12%; 36/297) (P = 0.30). Three twin pregnancies occurred in the GnRH antagonist group and two twin pregnancies in the placebo group.

CONCLUSIONS

Adding a GnRH antagonist in cycles with MOH in an IUI program does not increase live birth rates.

Dutch Trial Register no: NTR497.

Relationship between quality of life and distress in infertility: a validation study of the Dutch FertiQoL

BACKGROUND

This study examined the relationship between emotional distress as measured by the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL) questionnaire.

METHODS

The FertiQoL and HADS were distributed to a random sample of 785 patients attending 29 Dutch clinics for medically assisted reproduction. FertiQoL was psychometrically tested for reliability. Pearson's correlations were calculated between subscales of FertiQoL and HADS. Using an independent t-test, differences between patient subgroups were computed for both instruments. The threshold for clinically meaningful depression/anxiety on the HADS subscales was used to ascertain the critical threshold for high distress on the FertiQoL scales.

RESULTS

FertiQoL and HADS were completed by 583 patients (response 74%). Reliability of FertiQoL scales was high (reliability coefficient between 0.72 and 0.91). Significant negative correlations were found between FertiQoL subscales and HADS scores for anxiety and depression, ranging from –0.29 to –0.71. Means on FertiQoL scales and HADS scales of couples undergoing an assisted reproductive technology (ART) treatment and a non-ART treatment did not differ significantly. Patients scoring above the HADS threshold for pathology on anxiety had an average FertiQoL score of 58.8, whereas patients exceeding the HADS depression threshold had a FertiQoL total score of 51.9 (range 0–100).

CONCLUSIONS

Our study confirms the expected negative relation between quality of life as measured by FertiQoL and anxiety and depression. The data support that FertiQoL reliably measures QoL in women facing infertility. FertiQoL enables clinicians to tailor care more specifically to the patient in a comprehensive way.