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Journal: Human reproduction (Oxford, England)


Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children?

Concepts: Family


Is sugar-sweetened beverage (SSB) consumption associated with age at menarche?

Concepts: Menarche


Is post-natal growth during the first 2 years of life in IVF singletons affected by type of medium used for culturing human embryos during an IVF treatment?

Concepts: Childbirth, Reproduction, Religion


STUDY QUESTION: Is thin endometrium unresponsive to standard treatments expandable by intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF)? SUMMARY ANSWER: This cohort study is supportive of the effectiveness of G-CSF in expanding chronically unresponsive endometria. WHAT IS KNOWN ALREADY: In a previous small case series, we reported the successful off-label use of G-CSF in four consecutive patients, who had previously failed to expand their endometria beyond 6.9 mm with the use of standard treatments. STUDY DESIGN, SIZEAND DURATION: In a prospective observational cohort pilot study over 18 months, we described 21 consecutive infertile women with endometria <7 mm on the day of hCG administration in their first IVF cycles at our center. All previous cycles using traditional treatments with estradiol, sildenafil citrate (Viagra™) and/or beta-blockers had been unsuccessful. G-CSF (Nupogen™) was administered per intrauterine catheter by slow infusion before noon on the day of hCG administration. If the endometrium had not reached at least a 7-mm within 48h, a second infusion was given following oocyte retrieval. Primary and secondary main outcomes were an increase in endometrial thickness and clinical pregnancy, respectively. Endometrial thickness was assessed by vaginal ultrasound at the most expanded area of the endometrial stripe. PARTICIPANTS/MATERIALS, SETTINGS AND METHOD: This study was uncontrolled, each patient serving as her own control in a prospective evaluation of endometrial thickness. The mean ± SD age of the cohort was 40.5 ± 6.6 years, gravidity was 1.8 ± 2.1 (range 0-7) and parity was 0.4 ± 1.1 (range 0-4); 76.2% of women had, based on age-specific FSH and anti-Müllerian hormone, an objective diagnosis of diminished ovarian reserve and had failed 2.0 ± 2.1 prior IVF cycles elsewhere. MAIN RESULTS AND THE ROLE OF CHANCE: With 5.2 ± 1.9 days between G-CSF perfusions and embryo transfers, endometrial thickness increased from 6.4 ± 1.4 to 9.3 ± 2.1 mm (P < 0.001). The Δ in change was 2.9 ± 2.0 mm, and did not vary between conception and non-conception cycles. A 19.1% ongoing clinical pregnancy rate was observed, excluding one ectopic pregnancy. LIMITATIONS AND REASONS FOR CAUTION: Small sample size (but a highly selected patient population) in an uncontrolled cohort study and in unselected first IVF cycles at our center. WIDER IMPLICATIONS OF THE FINDINGS: This pilot study supports the utility of G-CSF in the treatment of chronically thin endometrium and suggests that such treatment will, in very adversely affected patients, result in low but very reasonable clinical pregnancy rates. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Foundation for Reproductive Medicine, New York, New York, USA, a not-for-profit research foundation and intramural grants from the Center for Human Reproduction (CHR)-New York. N.G. and D.H.B. are members of the board of the Foundation for Reproductive Medicine. N.G. is owner of CHR-New York, where the study was conducted. N.G. and D.H.B. have been recipients of research awards, travel grants and speaker honoraria from various pharmaceutical and medical device companies. None of these companies was, however, in any way associated with the materials and the manuscript presented here. N.G. and D.H.B. are listed as co-inventors on a number of awarded and still pending U.S. patents, none related to the materials presented here. N.G. is on the board of a medically related company, not in any way associated with the data presented here.

Concepts: Cohort study, Pregnancy, Clinical trial, Embryo, Uterus, Menstrual cycle, Endometrium, Granulocyte colony-stimulating factor


Two Australian government inquiries have recently called for the release of information to donor-conceived people about their gamete donors. A national inquiry, recommended ‘as a matter of priority’ that uniform legislation to be passed nationwide. A state-based inquiry argued that all donor-conceived people should have access to information and called for the enactment of retrospective legislation that would override donor anonymity. This paper responds to an opinion piece published in Human Reproduction in October 2012 by Professor Pennings in which he criticized such recommendations and questioned the motives of people that advocate for information release. I answer the arguments of Pennings, and argue that all parties affected by donor conception should be considered, and a compromise reached. The contact veto system is one such compromise. I discuss the education and support services recommended by the Victorian government and question Pennings' assertions that legislation enabling information release will lead to a decrease in gamete donation. Finally, I rebut Pennings' assertion that there is a ‘hidden agenda’ behind the call for information release. There is no such agenda in my work. If there is from others, then it is their discriminatory views that need to be addressed, not the move toward openness and honesty or the call for information by donor-conceived people.

Concepts: Reproduction, Critical thinking, Organ donation, Logic, Argument, Inquiry, Arguments, Human reproduction


What is the expression pattern of microRNAs (miRNAs) in human cumulus-oocyte complexes (COCs)?

Concepts: MicroRNA, Complex, Complexity


Does unilateral volume-adjusted laparoscopic diathermy increase the chances of ovulation in women with polycystic ovary syndrome (PCOS)?

Concepts: Estrogen, Luteinizing hormone, Syndromes, Menstrual cycle, Gynecology, Polycystic ovary syndrome



STUDY QUESTION: Is the placental burden of organotin compounds (OTCs) associated with congenital cryptorchidism in infant offspring from Finland and Denmark? SUMMARY ANSWER: Increasing concentrations of OTCs had a negative association with cryptorchidism in Finland, whereas a positive association was found in Denmark. WHAT IS KNOWN ALREADY: The rapid increase in the prevalence of cryptorchidism suggests that environmental factors, such as endocrine disruptors, may be involved. OTCs are endocrine disruptors at very low concentrations due to activation of the retinoid X receptor (RXR). STUDY DESIGN, SIZE, DURATION: Between the years 1997 and 2001, placentas from mothers of cryptorchid boys and from healthy controls were collected from Denmark (39 cases, 129 controls) and Finland (56 cases, 56 controls). In Denmark 33 and 6 boys, and in Finland 22 and 34 boys had mild or severe cryptorchidism, respectively. The association between concentrations of four OTCs [monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT) and triphenyltin (TPhT)] and case-control status was estimated. PARTICIPANTS/MATERIALS, SETTING, METHODS: In both countries, placenta samples were selected from larger cohorts. In Finland placenta samples were collected from boys with cryptorchidism at birth and matched controls (nested case-control design). Matching criteria were parity, maternal smoking (yes/no), diabetes (yes/no), gestational age (±7 days) and date of birth (±14 days). Numbers of controls per case was 1. In Denmark, all available placentas from cryptorchid boys were chosen and control placentas were selected randomly from the total Danish cohort (case-cohort design). The average number of controls per case was 3.3. OTCs in placenta samples were analysed with liquid extraction, ethylation and gas chromatography-mass spectrometry determination and coded by country-specific tertiles. MAIN RESULTS AND THE ROLE OF CHANCE: Generally, the concentrations of OTCs were very low. For most analytes, a large proportion of samples (29-96% depending on the country and case-control status) had OTC concentrations below the limit of quantification (LOQ). As an exception, the concentration of TBT was >LOQ in 99% of Finnish placentas. The mean concentrations of DBT and TBT were 1.5 and 7 times higher in Finland than in Denmark, respectively. For DBT in Danish placentas, the odds ratio (OR) for cryptorchidism in the second tertile (0.10-0.14 ng/g) when compared with the first tertile (<0.10 ng/g,

Concepts: European Union, Measurement, Placenta, Denmark, Swedish language, Scandinavia, Nordic countries, Organotin chemistry


STUDY QUESTION: What is the risk of relapse for women with endometrial hyperplasia treated with levonorgestrel-releasing intrauterine system (LNG-IUS) or oral progestogens? SUMMARY ANSWER: Relapse of complex endometrial hyperplasia after initial regression occurs often and it occurs less often in women treated with LNG-IUS than with oral progestogens. WHAT IS KNOWN ALREADY: The LNG-IUS and oral progestogens are used to treat women with endometrial hyperplasia and achieve regression. There is uncertainty over whether further surveillance for these women is necessary as the risk for relapse is unknown. STUDY DESIGN, SIZE, DURATION: A cohort study of 219 women with complex non-atypical or atypical endometrial hyperplasia who were treated and achieved initial regression with LNG-IUS (n = 153) or oral progestogens (n = 66) from August 1998 until December 2007 and followed up for >5 years. The mean length of follow-up was 74.7 ± SD 31.8 months for the LNG-IUS versus 87.6 ± SD 42.2 months for the oral progestogen group. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the proportion of women who relapsed or had hysterectomy after initial regression with LNG-IUS compared with oral progestogens by logistic regression and adjusting for confounding. The time from regression to relapse was explored through a survival analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Relapse of hyperplasia occurred in 13.7% (21/153) of women treated with LNG-IUS compared with 30.3% (20/66) of women treated with oral progestogens [adjusted odds ratio (OR) = 0.34, 95% confidence interval (CI): 0.17-0.7, P = 0.005]. Relapse rates over long-term follow-up were lower for complex non-atypical hyperplasia compared with atypical hyperplasia for both LNG-IUS (12.7%, 18/142 versus 27.3%, 3/11, respectively; P ≤ 0.001) and oral progestogens (28.3%, 17/60 versus 50%, 3/6, respectively; P ≤ 0.001). The survival analysis indicates that relapse occurred less often with LNG-IUS at 12, 24, 36, 48, 60 and >60 months of follow-up (hazard ratio 0.37, 95% CI: 0.2-0.7, P = 0.0013). There were no events of relapse after 48 months from regression with oral progestogens, but 5 women treated with LNG-IUS relapsed after 60 months when treatment was discontinued. Hysterectomy rates were lower in the LNG-IUS than oral progestogen group during follow-up (19.6%, 30/153 versus 31.8%, 21/66, respectively, OR = 0.52, 95% CI: 0.27-1, P = 0.05). Endometrial cancer was diagnosed in 2 (11.8%) women who had hysterectomy (n = 17) because of relapse. LIMITATIONS, REASONS FOR CAUTION: We are unable to accurately estimate the cancer risk in women who relapse during follow-up as only 17 out of 41 who relapsed underwent hysterectomy. WIDER IMPLICATIONS OF THE FINDINGS: Relapse of endometrial hyperplasia after initial regression occurs often and long-term follow-up is advised. STUDY FUNDING/COMPETING INTEREST(S): Ioannis D. Gallos and this study were funded through a grant from Wellbeing of Women (ELS022). No competing interests.

Concepts: Cohort study, Menopause, Estrogen, Relative risk, Odds ratio, Endometrial cancer, Endometrial hyperplasia, Hyperplasia