Secondary azoospermia after a successful natural pregnancy: a primary prospective study.

BACKGROUND: To date, there is a lack of studies conducted on males with secondary azoospermia as a potential cause of male infertility who had previously fathered children through natural conception. The current study aims to investigate the potential causes of secondary azoospermia as a presentation of male infertility as well as the prognostic factors that can impact sperm retrieval rate (SRR) while undergoing microdissection testicular sperm extraction (microTESE). RESULTS: Thirty two patients were recruited from the andrology outpatient clinic from August 2023 till January 2024. The mean age of the patients was sixty-two years old. All patients had varicoceles. Twenty seven patients (84%) had palpable varicocele grade 2 and 3 on both sides. Further multivariate logistic regression analysis of the significant factors in the univariate regression revealed that younger age (OR 0.7, 95% C.I. 0.7-1.0, p = 0.03) and having a history of coronary artery disease (CAD) were predictable factors for negative TESE outcome (OR 123.1, 95% C.I. 3.2-4748.5, P = 0.01). CONCLUSION: It appears that the etiopathogenesis of secondary azoospermia are multifactorial. Varicocele and CAD are major factors to be considered. Future studies should be implemented deploying larger pools of patients suffering from the same condition to affirm the findings of this primary study.

RéSUMé: CONTEXTE: À ce jour, il existe un manque d'études menées chez des hommes atteints d'azoospermie secondaire comme cause potentielle d'infertilité masculine, alors qu'ils avaient déjà engendré des enfants par conception naturelle. La présente étude vise à étudier les causes potentielles de l'azoospermie secondaire en tant que présentation de l'infertilité masculine, ainsi que les facteurs pronostiques qui peuvent avoir un impact sur le taux de récupération des spermatozoïdes (SRR) lors de l'extraction de spermatozoïdes testiculaires par microdissection (microTESE). RéSULTATS: Trente-deux patients ont été recrutés dans la clinique ambulatoire d'Andrologie d'août 2023 à janvier 2024. L'âge moyen des patients était de soixante-deux ans. Une varicocèle était présente chez tous les patients. Vingt-sept patients (84%) présentaient une varicocèle palpable de grade 2 et trois une varicocèle bilatérale. Une analyse par régression logistique multivariée des facteurs significatifs lors de la régression univariée a révélé qu'avoir un âge plus jeune (OR 0,7, IC à 95 % 0,7-1,0, p = 0,03) et des antécédents de maladie coronarienne (coronaropathie) étaient des facteurs prédictifs d'un résultat négatif à la microTESE (RC 123,1,95 % IC 3,2-4748,5, p = 0,01). CONCLUSIONS: Il apparaît que l'étiopathogénie de l'azoospermie secondaire est multifactorielle. La varicocèle et la coronaropathie sont des facteurs majeurs à prendre en compte. De futures études devraient être mises en œuvre en déployant des groupes de patients plus nombreux présentant la même affection pour confirmer les résultats de cette étude primaire.

Successful live birth in women with partial 17α-hydroxylase deficiency: report of two cases.

RESEARCH QUESTION: Can women with partial 17α-hydroxylase deficiency (17-OHD) conceive naturally with adequate hormonal control and endometrial preparation? DESIGN: This report presents two cases of women with partial 17-OHD who achieved successful pregnancies. The first case involved a 27-year-old Chinese woman with recurrent cysts and infertility, and the second case involved a 32-year-old Chinese woman with a complex disorder requiring IVF. Both cases were treated with oral prednisone to control hormone concentrations and underwent endometrial preparation. RESULTS: In the first case, the patient resumed spontaneous ovulation, conceived naturally, and gave birth to a healthy baby. In the second case, after cryopreserving embryos due to a thin endometrium, the patient underwent frozen embryo transfer and achieved a singleton pregnancy. CONCLUSION: This study suggests that women with partial 17-OHD can conceive naturally with appropriate hormonal management and endometrial preparation. These findings provide valuable insights into the reproductive potential of women with this disorder, and highlight the importance of further research in this area.

A comprehensive study of pre-eclampsia in IVF and natural conceptions: clinical phenotypes, perinatal outcomes and neonatal echocardiography.

RESEARCH QUESTION: What differences exist in the phenotypes of pre-eclampsia, perinatal outcomes and neonatal echocardiography between pregnancies conceived naturally and through IVF? DESIGN: Six hundred and ten women diagnosed with pre-eclampsia between January 2002 and December 2022 were included in this study. This research was conducted within the IVF and Maternal-Fetal Medicine Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan. Participants were divided into two groups: those who achieved pregnancy through IVF, and those who conceived naturally. The phenotypes of pre-eclampsia and perinatal outcomes were assessed using a propensity-matched sample (n = 218), along with neonatal echocardiography. RESULTS: After conducting propensity score matching, the natural conception group had a higher prevalence of early-onset pre-eclampsia (53.9% versus 37.7%, P = 0.04) and exhibited more severe features of pre-eclampsia (89.1% versus 69.8%, P = 0.01) compared with the IVF group. Regarding perinatal outcomes, neonates in the IVF group had higher placental weights compared with the natural conception group (580 versus 480 g, P = 0.031). The prevalence of abnormal findings on neonatal echocardiography was similar between the groups. Multivariate analysis showed that greater gestational age at delivery reduced the likelihood of abnormal findings on echocardiography [adjusted risk ratio (aRR) 0.950, P = 0.001], while pregestational diabetes mellitus increased the likelihood of abnormal findings (aRR 1.451, P = 0.044). Septal defects were the most common type of defect, occurring in 16.1% of infants. CONCLUSION: The impact of IVF conception on the severity of pre-eclampsia is not as expected. Neonatal echocardiography revealed a higher prevalence of abnormalities in offspring of women with pre-eclampsia compared with the general population. However, these issues were not linked to the method of conception, suggesting the existence of undisclosed factors that could influence the clinical features and perinatal outcomes of pre-eclampsia.

Intermittent spontaneous ovulation in patients with premature ovarian failure: Three case reports and review of literature.

BACKGROUND: Premature ovarian failure (POF) is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol (E2) levels and a minimal probability of pregnancy. This increases the physical and psychological burden experienced by young women of reproductive age, particularly with regards to over-diagnosis. CASE SUMMARY: Here, we report three cases (29, 22, and 33 years-of-age) diagnosed with POF after experiencing secondary amenorrhea for more than one year, serum levels of follicle-stimulating hormone (FSH) > 40 IU/L on two occasions with an interval of more than 4 wk, and negative progesterone withdrawal tests. All three patients were intermittently administered with drugs to create an artificial cycle. During the subsequent discontinuation period, the patients experienced intermittent follicular growth and spontaneous ovulation. One patient experienced two natural pregnancies (both with embryo arrest). CONCLUSION: Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development, ovulation, and even natural pregnancy. Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements, genetic risks and hypoestrogenic symptoms as soon as possible.

The pregnancy outcomes in patients with epididymal obstructive azoospermia after microsurgical vasoepididymostomy: a systematic review and meta-analysis.

Purpose: Pregnancy outcomes (overall patency rate, overall pregnancy rate, natural pregnancy rate, and the ratio of patients with pregnancy by assisted reproductive technology) after microsurgical vasoepididymostomy (MVE) in patients with epididymal obstructive azoospermia (EOA) were assessed through meta-analysis. Method: We searched PubMed, Embase, Web of Science, and the Cochrane Library databases up to 28 September 2022 for published literature related to retrospective or prospective clinical studies of obstructive azoospermia after apparent microsurgical vasoepididymostomy. Our search terms included obstructive azoospermia, epididymis obstruction, epididymal obstruction and vasoepididymostomy, and epididymovasostomy. Two researchers independently performed the literature search and assessed the eligibility of selected studies according to established inclusion criteria. The meta-analysis was performed using RevMan 5.4 software. Result: A total of 504 patients with EOA were included in 10 studies (including 2 prospective clinical studies and 8 retrospective clinical studies). The mean patency rate after MVE was 72% (95% CI 68-76%). The overall pregnancy rate was 34% (95% CI 30-38%). The natural pregnancy rate is 21% (95% CI 17-24%). The ratio of patients with pregnancy by assisted reproductive technology (ART) was 34.9%. For the factors affecting pregnancy outcomes after MVE, the overall pregnancy rates in patients receiving bilateral MVE were significantly higher than those receiving unilateral MVE (75.4 vs. 24.6%). The mean best sperm count and sperm motility in patients with overall pregnancy were significantly higher than those with failing pregnancies. For the subgroup meta-analysis of microsurgical vasoepididymostomy, there were no statistically significant differences in the overall patency rate (68 vs. 70%), the overall pregnancy rate (33 vs. 37%), the natural pregnancy rate (20 vs. 23%), the ratio of ART (30 vs. 28%) in end-to-side or end-to-end anastomosis, and longitudinal or triangular intussusception MVE. Conclusion: Vasectomy patency rates are higher, but natural pregnancy rates are lower in EOA male infertility patients after MVE. Altering the MVE procedures alone does not significantly improve pregnancy outcomes, but ART after MVE could improve the chance of pregnancy regardless of sperm parameters. We recommended that human sperms from EOA male infertility patients should be cryopreserved during intraoperative MVE for application in the subsequent ICSI treatment procedure.

Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: Results from a multicenter case-control study.

BACKGROUND: Sperm DNA fragmentation was hypothesized to have a role in the pathogenesis of recurrent pregnancy loss. Unfortunately, the quality of already published evidence is low. OBJECTIVES: To investigate the association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss by limiting, as much as possible, the interference of confounding factors. MATERIALS AND METHODS: This was a retrospective multicenter case-control study conducted in two Italian University Hospitals (i.e., Policlinico Gemelli, Rome and Humanitas S. Pio X, Milan) from July 2020 to March 2022. Cases were men belonging to couples affected by first trimester idiopathic recurrent pregnancy loss, defined as the previous loss of two or more pregnancies. Two control groups were selected: (i) men belonging to couples with proven fertility (i.e., at least two previous full-term pregnancies) (control group A); (ii) men belonging to couples with proven infertility (i.e., the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse) (control group B). The sperm DNA fragmentation index was measured by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: We included 74 cases, 37 men with proven fertility (control group A) and 100 men belonging to infertile couples (control group B). The median sperm DNA fragmentation index was significantly lower in control group A (17%, interquartile range: 14.3%-20.6%) compared to both case group (24.5%, interquartile range: 17%-32%; p < 0.0001) and control group B (24%, interquartile range: 18.9%-30%; p = 0.001). The rate of subjects with sperm DNA fragmentation index greater than 30% was significantly higher in both case groups (28%, 95% confidence interval [18%-40%]) and control group B (26%, 95% confidence interval [18%, 36%]) compared to control group A (0%, 95% confidence interval [0%-10%]) (p < 0.001). Multivariate regression models yielded a significant association between sperm DNA fragmentation index and recurrent pregnancy loss (adjusted odds ratio 1.13, 95% confidence interval [1.04-1.23], p = 0.006), but failed to show an association between sperm DNA fragmentation index and infertility (adjusted odds ratio 1.13, 95% CI [1-1.29], p = 0.05). CONCLUSIONS: Men within couples affected by recurrent pregnancy loss or infertility had a significantly higher rate of sperm DNA fragmentation compared to fertile controls. However, after adjusting for covariates, sperm DNA fragmentation index was associated only with recurrent pregnancy loss.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

Current progress on the curative effects of vasoepididymostomy for patients with obstructive azoospermia: An updated systematic review and meta-analysis of human studies.

BACKGROUND: Obstructive azoospermia (OA) is an important cause of male infertility, and epididymal OA (EOA) is a common disease. Microsurgical reconstruction is a common technique used in the treatment of EOA. In the present study, we analyzed the effectiveness of microsurgical vasoepididymostomy (MVE) at different levels and compared the differences among several MVE techniques. MATERIALS AND METHODS: A literature search was conducted in the PubMed, Web of Science, and Embase databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The included studies were published in English until May 14, 2021. The R 4.1.2 software was utilized to evaluate the event rate, risk ratio (RR), and 95% confidence interval (CI). RESULTS: A total of 51 studies involving 2853 patients with OA were included in our meta-analysis. The overall mean patency rate of patients who underwent MVE was 67.20% (95% [CI]:63.30%-71.10%), and the overall mean natural pregnancy rate of their partners was 40.05% (95% [CI]: 35.30%-45.60%). The pooled results showed that the patency rate of bilateral MVE was higher than that of unilateral MVE (RR = 1.42; 95% [CI]:1.25-1.61; p < 0.00). A comparison of the anastomotic site of MVE showed that the caudal/corpus area was favorable for the patency rate (RR = 1.17; 95% [CI]:1.04 - 1.32; p < 0.00). The caudal area was also advantageous for the patency rate (RR = 1.20; 95% CI:1.03 - 1.41; p < 0.04). Compared with typical MVE (65.20%, 95% [CI]:61.40%-69.10%), deferential vessel-sparing MVE with a higher overall mean patency rate (83.60%, 95% [CI]:75.40%-91.70%). CONCLUSIONS: The meta-analyses indicated that MVE is a high- and cost-effective therapeutic method for patients with EOA, and deferential vessel-sparing MVE could be mainstream in the near future.

A model established for predicting natural pregnancy possibility based on the imaging characteristics of 4-dimensional hysterosalpingo-contrast sonography. / åŸºäºŽå››ç»´è¶ å£°å­å®«è¾“åµç®¡é€ å½±çš„å½±åƒå­¦ç‰¹å¾å»ºç«‹è‡ªç„¶å¦Šå¨ é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: The incidence of infertility is increasing, more than 30% of them having related abnormal tubal patency. Four-dimensional (4D) hysterosalpingo-contrast sonography (HyCoSy) overcomes the shortcomings of 3D HyCoSy in the diagnosis of tubal patency, showing high specificity and accuracy. In addition, 4D HyCoSy discards iodine allergy and X-ray radiation and possesses easy-operating, contributing to good acceptance in clinical practice. However, there is no research to explore the imaging standards related to the possibility of natural pregnancy after 4D HyCoSy. If a predictive model of postoperative natural pregnancy was established using the analysis of clinical data combined with imaging characteristics of 4D HyCoSy of patients with tubal factor infertility, clinical decision-making can be wisely guided in the future. This study aims to establish a predictive model of natural pregnancy after 4D HyCoSy based on clinical data and imaging characteristics of patients with tubal factor in fertility. METHODS: A retrospective study was conducted for patients who were diagnosed with tubal factor infertility in Hunan Guangxiu Hospital from February 2017 to May 2018. The patients ought to possess complete 4D HyCoSy imaging data and at least one-side-unobstructed fallopian tube. General clinical data and imaging data were collected. Pregnancy outcome was followed up till 3 months after 4D HyCoSy. According to pregnancy outcome, patients were divided into a pregnancy group and a non-pregnancy group. Binary logistic regression was used to analyze the correlation between various variables and natural pregnancy after 4D HyCoSy. The variables with significant difference (P<0.05) in single-factor logistic regression were included in the natural pregnancy probability prediction model. The classification accuracy was further verified with 10-fold cross-validation. RESULTS: A total of 1 085 patients with clinically suspected tubal factor infertility who met the requirements and followed the doctors' prescription were collected. Clinical characteristics (age and duration of infertility) and 4D HyCoSy imaging characteristics (thickness of endometrium from the 3rd to the 7th day after the end of menstruation, visualization of the left fallopian tube, the diffusion of contrast agent around the left ovary, and the diffusion of contrast agent around the right ovary) were independent predictors for natural pregnancy 3 months after 4D HyCoSy. A natural pregnancy probability prediction model was established with the area under the curve (AUC) verified by the 10-fold cross-validation all greater than 0.75, and the best AUC was 0.868. The Q value obtained by the prediction model was the probability of natural pregnancy, and the cutoff value was 0.5. When the Q value was greater than 0.5, it was recommended to attempt natural pregnancy for 3 months, and when the Q value was less than 0.5, in vitro fertilization was adviced. CONCLUSIONS: A predictive model for the evaluating probability of natural pregnancy in women with tubal factor infertility after 4D HyCoSy is successfully established based on the analysis for clinical data and imaging characteristics. This model shows a great potential in assisting clinical decision making.

Sperm DNA integrity and male infertility: a narrative review and guide for the reproductive physicians.

Background and Objective: Conventional semen analysis (SA) remains an essential tool in the initial male fertility evaluation and subsequent follow-up. However, it neither provides information about the functional status of spermatozoa nor addresses disorders such as idiopathic or unexplained infertility (UI). Recently, assessment of sperm DNA fragmentation (SDF) has been proposed as an extended sperm test that may help overcome these inherent limitations of basic SA. In this review, we aim to: (I) discuss the pathophysiological aspects of SDF, including natural repair mechanisms, causes, and impact on reproductive outcomes; (II) explain different assessment tools of SDF, and describe potential therapeutic options to manage infertile men with high SDF; and (III) analyse the strengths, weaknesses, opportunities and threats (SWOT) of current research on the topic. Methods: This review was constructed from original studies, systematic reviews and meta-analyses that were published over the years up until August 2021, related to the various aspects of SDF. Key Content and Findings: Different mechanisms lead to high SDF, including defective chromatin packaging, apoptosis, and seminal oxidative stress. The relevance of sperm DNA integrity to male fertility/infertility has been supported by the frequent observation of high levels of SDF in infertile men, and in association with risk factors for infertility. Additionally, high SDF levels have been inversely correlated with the outcomes of natural pregnancy and assisted reproduction. Terminal deoxynucleotidyl transferase dUTP nick end labelling, sperm chromatin structure assay, sperm chromatin dispersion, and Comet assay are four commonly used assays for measurement of SDF. Addressing lifestyle risks and underlying conditions, antioxidants, hormonal therapy, and advanced sperm selection techniques have all been proposed as potential therapeutic options to lower SDF. Conclusions: The sum of literature provides evidence of detrimental effects of high SDF on both natural and assisted fertility outcomes. Standardization of the techniques used for assessment of SDF and their incorporation into the work up of infertile couples may have significant implications on the future management of a selected category of infertile men with high SDF.

[Influence of different treatments of unilateral testicular torsion on the long-term fertility of the patient].

OBJECTIVE: To evaluate the effects of different treatments of unilateral testicular torsion on the long-term fertility of the patient. METHODS: We reviewed the clinical and fertility-related follow-up data on 92 cases of unilateral testicular torsion treated by orchiectomy (the OE group, n = 49) or orchiopexy (the OP group, n = 43) between January 2000 and December 2014. We compared the testis volume, semen parameters, reproductive hormone indexes, natural pregnancy rate (NPR) and time to pregnancy (TTP) between the two groups, and analyzed the influence of orchiectomy and orchiopexy on the fertility of the patients. RESULTS: Totally, 77 of the men met the inclusion criteria and included in this study, 40 in the OE and 37 in the OP group. Follow-up data exhibited no statistically significant difference between the two groups of patients in the age of marriage, mean frequency of intercourse or sexual function. The men in the OE group, compared with those in the OP group, showed a larger volume of the opposite testis (ï¼»17.62 ± 2.15ï¼½ vs ï¼»16.86 ± 2.05ï¼½ ml, P > 0.05), but lower semen volume (ï¼»4.09 ± 0.89ï¼½ vs ï¼»4.11 ± 0.76ï¼½ ml, P > 0.05), sperm concentration (ï¼»27.60 ± 7.58ï¼½ vs ï¼»27.74 ± 6.80ï¼½ ×106/ml, P > 0.05), sperm motility (ï¼»60.14 ± 14.50ï¼½% vs ï¼»60.29 ± 16.36ï¼½%, P > 0.05), and percentages of progressively motile sperm (PMS) (ï¼»38.37 ± 10.88ï¼½% vs ï¼»38.82 ± 9.73ï¼½%, P > 0.05) and morphologically abnormal sperm (MAS) (ï¼»29.80 ± 7.29ï¼½% vs ï¼»29.55 ± 7.03ï¼½%, P > 0.05), lower levels of FSH (ï¼»8.01 ± 2.31ï¼½ vs ï¼»8.12 ± 2.63ï¼½ IU/L, P > 0.05), LH (ï¼»15.05 ± 4.20ï¼½ vs ï¼»15.46 ± 4.76ï¼½ IU/L,P > 0.05) and T (ï¼»19.06 ± 3.60ï¼½ vs ï¼»19.46 ± 4.02ï¼½ nmol/L, P > 0.05), lower NPR (75.0% ï¼»30/40ï¼½ vs 83.8% ï¼»31/37ï¼½, P > 0.05) and longer TTP (ï¼»18.0 ± 5.7ï¼½ vs ï¼»14.6 ± 3.8ï¼½ mo, P > 0.05). CONCLUSIONS: For patients with unilateral testicular torsion, orchiectomy achieved a lower semen quality and NPR and a longer TTP than orchiopexy, but induced no significant fertility decrease. Detorsion of the torsioned testis little affects the fertility of the patient.

Obstetric and perinatal outcomes of in vitro fertilization and natural pregnancies in the same mother.

OBJECTIVE: To compare obstetric and perinatal outcomes between pregnancies conceived using in vitro fertilization (IVF) and natural pregnancies of the same women. DESIGN: This was a case-control study of deliveries between November 2008 and January 2020 in which each IVF pregnancy was matched to a natural pregnancy of the same woman (1:1 ratio). SETTING: University hospital. PATIENT(S): We included women with consecutive live singleton deliveries (>24 weeks of gestation) at the Edith Wolfson Medical Center. We excluded IVF pregnancies attained using egg donation. INTERVENTION(S): In vitro fertilization-attained pregnancies (as compared with natural ones). MAIN OUTCOME MEASURE(S): Primary outcome: preterm birth (PTB). SECONDARY OUTCOMES: small for gestational age (SGA) neonates and pregnancy-induced hypertension (PIH; gestational hypertension or pre-eclampsia). RESULT(S): A total of 544 IVF pregnancies were matched to 544 natural pregnancies, each in the same woman. In 292 women (53.7%), the natural pregnancy preceded the IVF pregnancy. Maternal age was significantly higher in IVF deliveries. Gestational age at delivery and the rates of PTB, PIH, instrumental delivery, cesarean delivery, and SGA neonates were comparable between IVF and natural pregnancies. Birth weight was slightly lower in IVF pregnancies. On multivariate analysis, IVF was not independently associated with PTB, SGA, or PIH after adjustment for confounders. CONCLUSION(S): When compared in a cohort of the same women, natural and IVF-attained pregnancies did not differ with regard to obstetric and perinatal outcomes.

In vitro fertilization and embryo transfer alter human placental function through trophoblasts in early pregnancy.

The mechanism underlying the potential risk associated with in vitro fertilization and embryo transfer (IVF­ET) has been previously investigated but remains to be fully elucidated. As the placenta is a critical organ that sustains and protects the fetus, this is an important area of research. The aim of the present study was to determine the difference in trophoblast cell function in the first trimester between naturally conceived pregnancies and pregnancies achieved via IVF­ET therapy. A total of 20 placental villi in first trimester samples were obtained through fetal bud aspiration from patients undergoing IVF­ET due to oviductal factors between January 2016 and August 2018. In addition, a further 20 placental villi were obtained from those who naturally conceived and had normal pregnancies but were undergoing artificial abortion; these patients were recruited as the controls. Reverse transcription­quantitative (RT­q)PCR and semi­quantitative immunohistochemical methods were used to detect the mRNA and protein expression of α­fetoprotein (AFP), vascular endothelial growth factor (VEGF), transferrin (TF), tubulin ß1 class VI (TUBB1), metallothionein 1G (MT1G), BCL2, glial cells missing transcription factor 1 (GCM1), epidermal growth factor (EGF) receptor (EGFR), PTEN and leukocyte associated immunoglobulin like receptor 2 (LAIR2) in villi from both groups. Differentially expressed genes were analyzed using Search Tool for the Retrieval of Interacting Genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted. The RT­qPCR data revealed that the mRNA expression levels of AFP, VEGF and TF were significantly higher in the IVF­ET group than in the control group (P<0.05), and those of TUBB1, MT1G, BCL2, GCM1, EGFR, PTEN and LAIR2 were significantly lower (P<0.05). These gene products were expressed in the placental villus tissues, either in the cytoplasm, or in the membrane of syncytiotrophoblast and cytotrophoblast cells. The immunohistochemistry results were in line with those observed using RT­qPCR. KEGG pathway analysis indicated that the trophoblast cell function of the IVF­ET group in the first trimester was different from naturally conceived pregnancies with regard to proliferation, invasion, apoptosis and vascular development. The IVF­ET process may trigger adaptive placental responses, and these compensatory mechanisms could be a risk for certain diseases later in life.

Natural Pregnancy Seeking in Subfertile Women with Endometriosis.

Several pathogenetic mechanisms have been postulated to explain the association between endometriosis and subfertility. However, to date, definitive conclusions cannot be drawn. In this study, we hypothesized that the reduced exploitation of the natural chances of conception could be an additional detrimental factor. Due to dyspareunia or the need for hormonal treatment to temper pelvic pain, one may expect affected women to exploit less the chances of natural pregnancy. In this cross-sectional study of 292 women undergoing IVF, we investigated the severity of pelvic pain symptoms, the sexual function (using the Female Sexual Function Index [FSFI]), and the reproductive strategies of women with (n = 62) and without (n = 230) endometriosis. Basal clinical and demographic characteristics did not differ between the two groups. Conversely, all pelvic pain symptom scores were increased in women with endometriosis. Endometriosis patients also showed greater pain at the FSFI, but no other significant differences were detected as regards sexual function. The use of hormonal contraceptive agents did not differ between the study groups. Moreover, questions aimed at disentangle whether affected women exploited less the natural chances of pregnancy did not reveal any significant difference. In conclusion, this study does not support the hypothesis that women with endometriosis exploit less the chances of natural pregnancy, despite the presence of pelvic pain.

A novel protein biochip screening serum anti-sperm antibody expression and natural pregnancy rate in a follow-up study in Chinese infertility.

Production of anti-sperm antibody (ASA) often suffers from autoimmune reaction against sperms in human infertility. The antibodies are measured in both blood and seminal plasma of males. Here, we reported a simple protein biochip methodology that takes advantage of a functionalized self-assembled monolayer modified by N-hydroxysuccinimide (NHS) and enables identification of anti-sperm antibody in Chinese male infertility. To validate this biochip platform, we immobilized purified sperm protein on the biochip surface and tested a variety of parameters in quality controls for the protein assay, respectively. Then, we analyzed serum samples from 368 patients with infertility and 116 healthy donors by means of this biochip simultaneously. We found that positive rate of serum ASA was 20.92% (77/368) in the cases and 1.72% (2/116) in the controls, respectively. Furthermore, we further corroborated the biochip assay in comparison with ELISA method. We found that both methods were compatible for the detection of serum ASA in the patients. In addition, a follow-up study for natural conception in ASA-positive and ASA-negative patients was conducted. The result showed a significant correlation between serum ASA expression and natural pregnancy rate 6.5% in ASA-positive patients while 18.9% in ASA-negative patients, indicating the potential roles of ASA in naturally reproductive processes.

A Comparison of Postpartum Depression in Mothers Conceived by Assisted Reproductive Technology and Those Naturally Conceived.

BACKGROUND: It is thought that mothers who conceive via assisted reproductive technology (ART) may be at greater risk of postpartum depression (PPD) because of the problems and psychological stresses associated with ART treatment. The aim of the present study is to determine the occurrence of PPD among mothers who conceive by ART in comparison with those who naturally conceive. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. MATERIALS AND METHODS: This historical cohort study investigated 406 mothers with infants aged 3-9 months. Three hundred and eight women with natural pregnancies were selected as the control group from mothers who referred to Tehran healthcare centres for infant vaccinations. The ART group consisted of 98 women who conceived via ART at Royan Institute. Participants completed a general questionnaire that asked about education, occupation, number of children, delivery method, history of infant hospitalization, breastfeeding, mothers' and infants' ages, cause of infertility (ART group), and history of depression. A validated Persian version of the EPDS was used to measure depressive symptoms. RESULTS: The mean EPDS score in mothers who naturally conceived was 8.38 ± 0.35 in comparison with mothers who conceived via ART (7.59 ± 0.63). The proportions of women who reported PPD were 26.0% for the control group and 20.4% for the ART group. There was no statistically significant difference in PPD between the control and ART groups (P=0.26). CONCLUSION: The occurrence of PPD in mothers who conceived via ART was similar to those who conceived naturally.

Spontaneous ovarian hyperstimulation syndrome: Report of two cases.

BACKGROUND: Spontaneous ovarian hyperstimulation syndrome (sOHSS) is extremely rare. It can be divided into four types according to its clinical manifestations and follicle stimulating hormone receptor mutations. CASE SUMMARY: Here we report two cases of sOHSS in Chinese women, one with a singleton gestation developing sOHSS in the first trimester who conceived naturally and the other with a twin pregnancy developing sOHSS in the second trimester after a thawed embryo transfer cycle. Both patients were admitted to the hospital with abdominal distension, ascites, and enlarged ovaries. Conservative treatment was the primary option of management. The first patient had spontaneous onset labor at 40 wk of gestation and underwent an uncomplicated vaginal delivery of a male newborn. The second patient delivered a female baby and a male baby by caesarean section at 35 wk and 1 d of gestation. CONCLUSION: Patients with a history of ovarian hyperstimulation syndrome should be closely monitored. Single embryo transfer might reduce the risk of this rare syndrome.

Safe and successful birth following pelvic radiotherapy for rectal mucosa-associated lymphoid tissue lymphoma: a case report.

BACKGROUND: Mucosa-associated lymphoid tissue lymphomas can occur in various parts of the body, and half of mucosa-associated lymphoid tissue lymphomas occur in the gastrointestinal tract. Gastric mucosa-associated lymphoid tissue lymphoma is the most common lymphoma of the gastrointestinal tract and primary rectal mucosa-associated lymphoid tissue lymphoma is very rare. Because of the high radiosensitivity of mucosa-associated lymphoid tissue lymphomas, this condition can be controlled with radiotherapy of approximately 30 Gy alone. However, ovarian dysfunction as an adverse event of radiotherapy for pelvic lesions can become a problem in girls and women. We report a case of a 28-year-old woman with rectal mucosa-associated lymphoid tissue lymphoma who safely gave birth to a baby following 30.6 Gy radiotherapy to her whole rectum. CASE PRESENTATION: A 28-year-old Japanese woman became aware of bloody stools and was diagnosed as having Lugano I rectal mucosa-associated lymphoid tissue lymphoma. She was referred to our institute and initiated on radiotherapy. However, she expressed a desire to bear children. We used horizontally opposed pair fields for radiotherapy to minimize the irradiation to her endometrium and ovary. A total dose of 30.6 Gy was given in 17 fractions of 1.8 Gy by 10-Megavolt X-ray linear accelerator. As a result, one-third of her uterus and half of her ovary were outside the irradiation field. After approximately 1 year of treatment, positive pregnancy was confirmed and finally she safely gave birth to a baby girl without congenital abnormalities. CONCLUSIONS: This report provides hope for girls and women who have undergone irradiation for pelvic mucosa-associated lymphoid tissue lymphomas and who desire to bear children.

Cost-effectiveness of 'immediate IVF' versus 'delayed IVF': a prospective study.

STUDY QUESTION: How does the cost-effectiveness (CE) of immediate IVF compared with postponing IVF for 1 year, depend on prognostic characteristics of the couple? SUMMARY ANSWER: The CE ratio, i.e. the incremental costs of immediate versus delayed IVF per extra live birth, is the highest (range of €15 000 to >€60 000) for couples with unexplained infertility and for them depends strongly on female age and the duration of infertility, whilst being lowest for endometriosis (range 8000-23 000) and, for such patients, only slightly dependent on female age and duration of infertility. WHAT IS KNOWN ALREADY: A few countries have guidelines for indications of IVF, using the diagnostic category, female age and duration of infertility. The CE of these guidelines is unknown and the evidence base exists only for bilateral tubal occlusion, not for the other diagnostic categories. STUDY DESIGN, SIZE, DURATION: A modelling approach was applied, based on the literature and data from a prospective cohort study among couples eligible for IVF or ICSI treatment, registered in a national waiting list in The Netherlands between January 2002 and December 2003. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 5962 couples was included. Chances of natural ongoing pregnancy were estimated from the waiting list observations and chances of ongoing pregnancy after IVF from follow-up data of couples with primary infertility that began treatment. Prognostic characteristics considered were female age, duration of infertility and diagnostic category. Costs of IVF were assessed from a societal perspective and determined on a representative sample of patients. A cost-effectiveness comparison was made between two scenarios: (I) wait one more year and then undergo IVF for 1 year and (II) immediate IVF during 1 year, and try to conceive naturally in the following year. Comparisons were made for strata determined by the prognostic factors. The final outcome was a live birth. MAIN RESULTS AND THE ROLE OF CHANCE: The gain in live birth rate of the immediate IVF scenario versus postponed IVF increased with female age, and was independent from diagnostic category or duration of infertility. By contrast, the corresponding increase in costs primarily depended on diagnostic category and duration of infertility. The lowest CE ratio was just below €10 000 per live birth for endometriosis from age 34 onwards at 1 year duration. The highest CE ratio reached €56 000 per live birth for unexplained infertility at age 30 and 3 years duration, dropping to values below € 30 000 per live birth from age 32 onwards. It reached values below €20 000 per live birth with 3 years duration at age 34 and older. The CE ratio was in between for the three other diagnostic categories (i.e. Male infertility, Hormonal and Immunological/Cervical). LIMITATIONS, REASONS FOR CAUTION: We applied estimates of chances with IVF, excluding frozen embryos, for which we had no data. Therefore, we do not know the effect of frozen embryo transfers on the CE. WIDER IMPLICATIONS OF THE FINDINGS: The duration of infertility at which IVF becomes cost-effective depends, firstly, on the level of society's willingness to pay for one extra live birth, and secondly, given a certain level of willingness to pay, on the woman's age and the diagnostic category. In current guidelines, the chances of a natural conception should always be taken into account before deciding whether to start IVF treatment and at which time. STUDY FUNDING/COMPETING INTEREST(S): Supported by Netherlands Organisation for Health Research and Development (ZonMW, grant 945-12-013). ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none.

Prenatal screening at 11-13+6 weeks in assisted reproductive technology singleton pregnancies and those conceived naturally.

AIM: To investigate whether assisted reproductive technology (ART) increases the risk of fetal chromosomal abnormalities. METHODS: A total of 2034 singleton pregnant women were included in this retrospective study. They were divided into ART (574 fetuses) and control groups (1460 fetuses conceived naturally). All pregnant women received screening according to the Fetal Medicine Foundation, London 2004 Kypros H. Nicolaides guidelines at 11-13+6 weeks of gestation. Accordingly, women with value at risk of chromosomal abnormalities >1:250 underwent chorionic villus sampling or amniocentesis. RESULTS: Mean body mass index was 22.83 ± 3.27 versus 21.29 ± 2.81 kg/m(2) in the ART and control groups, respectively (P < 0.001). Mean maternal age was higher in the ART group (31.07 ± 4.30 vs 28.16 ± 3.99 years, P < 0.001). Crown-rump length (CRL) and biparietal diameter (BPD) were significantly higher in the ART group (P < 0.001), but free ß-human chorionic gonadotropin and plasma protein-A MoM were similar between the groups. Interestingly, nuchal translucency thickness in the ART group was significantly higher than in the control group, but the difference disappeared at 13-13+6 weeks. Positive ultrasound screening rate was not significantly different. The prevalence of high risk (3.83% vs 3.83%) and that of abnormal karyotype (0.35% vs 0.21%) were similar. CONCLUSIONS: Despite the negative factors associated with the infertile women themselves, ART did not seem to increase the risk of fetal chromosomal abnormalities. Additionally, fetus size in the ART group was bigger than that in the natural conception group.