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Tussen maart en juni 2009 ontvingen alle meisjes, geboren in 1996 en op het moment van het onderzoek woonachtig in 8 regio’s verspreid over Vlaanderen, in het kader van het Vlaamse cohortonderzoek JOnG! een semigestructureerde vragenlijst met onder meer vragen over de leeftijd van menarche, de kenmerken van hun menstruele cyclus en de eventuele impact ervan op hun sociale activiteiten. Van de 769 respondenten (dat is 15,7 % van de doelpopulatie in de betrokken regio’s) had 47,2 % reeds menstruaties. De gemiddelde leeftijd van menarche werd geschat op 12,9 ± 1,3 jaar. Van de 363 meisjes die reeds menstruaties hadden, ervoer 41,6 % (95 % BI 36,4–47,0 %) deze als pijnlijk tijdens de afgelopen 3 maanden. Uit het onderzoek blijkt een significante correlatie tussen pijnlijke menstruatie enerzijds (dysmenorroe), en jongere menarcheleeftijd (p <.05) en meer overvloedige menstruatie (p <.001) anderzijds. Bovendien ervoer één op vier 13-jarige meisjes een negatieve impact van menstruaties op hun schoolparticipatie en deelname aan sociale activiteiten. Deze proportie is echter significant groter bij meisjes met dysmenorroe (41,3 %) dan bij meisjes die hun menstruaties hebben zonder noemenswaardige klachten (14,2 %) (RR = 2,9; 95 % BI, 2,0–4,4; p< .001). Uit de resultaten van deze studie blijkt dat menstruatie-gebonden klachten frequent voorkomen bij jonge tienermeisjes, wat aandacht verdient vanwege jeugdgezondheidszorg.

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment cost. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of r-hFSH alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4,108–€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%−17% of the total costs of one ART cycle with one fresh ET leading to a live birth.

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation during assisted reproduction technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (RR 1.16 [1.05, 1.26]) and live birth (relative risk [RR] 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5–14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35–40 years with normal ovarian reserve.

(Abstracted from Hum Reprod2021;36:2676–2686)Although the adverse effect of endometriosis on pregnancy rate is well established, the impact of endometriosis on pregnancy rate after treatment with assisted reproductive technology (ART) remains unclear. There is evidence that the use of prolonged pituitary downregulation before ART in women with any degree of endometriosis increases the odds of clinical pregnancy significantly (up to 4-fold); however, this evidence is limited by potential methodology and publication bias.

BACKGROUND: A case–control study was designed to determine the possible association between chronic exposure to dioxins and polychlorinated biphenyls (PCBs), and the occurrence of endometriosis. The study group consisted of 42 infertile endometriosis cases and 27 mechanical infertile controls, both groups attending one of the collaborating Centres for Reproductive Medicine, enrolled between 1996–1998. METHODS: Exposure assessment to dioxin-like compounds was determined through CALUX (chemical-activated luciferase gene expression)-bioassay to measure dioxin-like total toxic equivalents (dioxins and co-planar PCBs), whereas non-co-planar PCBs were determined through chemical analysis. RESULTS: No association was found between median dioxin-like total toxic equivalents (TEQ) and the occurrence of endometriosis in infertile women [cases (n = 34): 29; controls (n = 27): 24; NS]. When patients were subdivided based on an arbitrary cut-off value of 100 pg TEQ/g serum lipids, no statistically significant association between very high exposure to dioxin-like compounds and endometriosis was found [crude odds ratio (OR) = 4.33; confidence interval (CI) 0.49–38.19; NS]. After adjusting for body mass index, and alcohol consumption, the risk increased slightly to OR = 4.6 (CI 0.48–43.62; NS). There was no confounding by age, ovulatory dysfunction, caffeine intake, smoking or exposure to non-co-planar PCBs. CONCLUSIONS: The study results showed no statistically significant association between exposure to dioxin-like compounds and the occurrence of endometriosis in infertile women.

A case-control study was designed to determine the possible association between chronic exposure to dioxins and polychlorinated biphenyls (PCBs), and the occurrence of endometriosis. The study group consisted of 42 infertile endometriosis cases and 27 mechanical infertile controls, both groups attending one of the collaborating Centres for Reproductive Medicine, enrolled between 1996-1998.

Mouse and human embryos, cultured in vitro, undergo a delay in development compared with those grown in vivo. This delay can be caused by suboptimal culture conditions, but possible influences of ovarian stimulation cannot be excluded. The objective of this study was to test the hypothesis that both in vitro and in vivo, preimplantation embryonic development and postimplantation fetal development are impaired in superovulated female mice when compared with naturally cycling controls. A delay in in-vitro blastocyst hatching and in-vivo blastocyst formation (P < 0.03 and P < 0.0001 respectively) and a 40% fetal growth retardation (P < 0.0001) were observed after superovulation in comparison with naturally cycling controls. After transfer to non-stimulated foster mothers, blastocysts from stimulated females had a lower implantation rate (P < 0.005), and developed into fewer living fetuses (P < 0.02), more resorption sites (P < 0.02) and had more pronounced growth retardation (P < 0.0001) when compared with blastocysts from naturally cycling controls. In conclusion, superovulation in the mouse causes a delayed embryonic development in vitro and in vivo, an increased abnormal blastocyst formation, a pronounced fetal growth retardation, and an increased number of resorption sites. If this observation in mice can be extrapolated to humans, it may offer an explanation for the delay in embryonic development and the low birth weight observed after IVF.

Abstract.: Background: This study was performed to test the hypothesis that endometriosis undergoes regression during pregnancy. Methods: This study was performed on 11 baboons with histologically proven endometriosis, housed at the Institute of Primate Research, Nairobi, Kenya. In each individual baboon paired laparoscopies were performed prior to and during pregnancy (6 during first and 5 during second trimester of gestation) with an interval of 5±3 months. During each laparoscopy the number, size and type of endometriosis implants were noted in detail on a pelvic map; the endometriosis score and stage were calculated according to the revised American Fertility Society (AFS) classification. In each baboon the observations prior to and during pregnancy were compared and analysed by Wilcoxon signed rank test (two-tailed). Results: No significant change was observed in the AFS score or stage of endometriosis, or in the number, size and type of endometriotic lesions in baboons during gestation when compared to the nonpregnant state. Conclusion: In baboons pregnancy had no significant effect on endometriosis during the first or second trimester of gestation.

The aim of this experiment was to design a suitable mouse model for male subfertility in which to study the effect of decreased sperm quality on embryo quality in vivo and in vitro. To achieve male subfertility, testes of adult male mice were immersed in water at either 42 degrees C (heated) or 33 degrees C (controls) during 20 min. Twenty-eight days after treatment, all heat stressed males showed a significant decrease in relative testis weight [384.7 mg in controls (286.7-460.6) versus 323 mg in stress heated groups (117.9-405.6); P < 0.001], sperm concentration [3.75 x 10(6)/ml (2.75-7.25) versus 1.00 x 10(6)/ml (0-4.00); P < 0.001] and progressive sperm motility [57.5% (48.0-79.0) versus 42.5% (14.0-66.0); P < 0.001]. Moreover, after mating to heat exposed males, not only the number of pregnant females (20/22 versus 18/30) but also the weight of their embryos [275.4 mg (78.7-339.4) versus 261.8 mg (68.1-339.0); P < 0.001] was significantly lower at 14.5 days post coitum when compared to controls. Neither the number of resorption sites nor the number of viable embryos per pregnant female was significantly different between groups. Also, the in-vitro fertilization rate of oocytes, fertilized by spermatozoa collected from heat stressed males, was significantly lower (44.9%; P < 0.0001) when compared to controls (65.1%; P < 0.0001). In conclusion, the results of this study suggest that male subfertility induced by acute scrotal heating may result in impaired sperm quality, reduced embryo weight in vivo and decreased fertilization rate in vitro.

This study was performed to test the hypothesis that anti-endometrial, lymphocyte-mediated cytotoxicity and natural killer (NK) activity are reduced in baboons with endometriosis when compared to animals with a normal pelvis. Lymphocyte-mediated cytotoxicity was determined in 28 baboons (15 with endometriosis, 13 with normal pelvis) and NK cell activity was evaluated in 42 baboons (31 with endometriosis, 11 with normal pelvis). Anti-endometrial lymphocyte-mediated cytotoxicity was determined by a 20 h assay with effector-target ratios of 50:1 and 25:1. The NK activity (K562 cell line as target) was simultaneously measured in all animals during a 4 h assay with effector:target ratios of 200:1, 100:1, 50:1, 25:1, 12:1, 6:1 and 3:1. Statistical analysis was performed using analysis of variance, paired rank, Mann-Whitney, Kruskal-Wallis and Fisher exact tests where appropriate. Lymphocyte-mediated cytotoxicity was significantly lower (P < 0.025) in baboons with endometriosis (mean 5.9 +/- 8.7%, median 0%, range 0-26%) than in animals with a normal pelvis (mean 22.9 +/- 23.0%, median 7%, range 0-78%). This difference could be explained by the absence of cytotoxicity in baboons with moderate to severe endometriosis, probably due to high spontaneous release of 51Cr from labelled target cells. When stricter criteria were used and only animals with a labelling index (maximal/spontaneous release) of > or = 1.7 were analysed (n = 11), the anti-endometrial cytotoxicity was comparable between baboons with and without endometriosis. NK cell activity was also comparable in primates with and without endometriosis. In conclusion, no difference in lymphocyte-mediated cytotoxicity and NK cell activity was observed between baboons with and without endometriosis.

The prevalence of spontaneous endometriosis was investigated by laparoscopy in 52 baboons (Papio anubis and Papio cynocephalus) of proven fertility. Clinical endometriosis was diagnosed in 9 (17%) and 4 (8%) baboons with or without a previous hysterotomy, respectively. Endometriosis was confirmed by histology in 75% of these animals. The 37 endometriotic lesions were classified as typical (13%), subtle (57%), or suspicious (30%); and the percentage of histological confirmation was 100%, 61%, and 50%, respectively. Lesions were found on the uterosacral ligaments and in Douglas' pouch (46%), on the uterine peritoneum and the uterovesical fold (38%), and on uterine-omental adhesions (11%). Only 5% of the lesions were localized on the ovarian ligament, whereas ovarian endometriosis was not found. This study for the first time demonstrates that spontaneous endometriosis occurs in healthy baboons with proven fertility. It also shows that the laparoscopic appearances, the histological aspect, and the localization of the pelvic lesions are comparable to those found in women. We therefore conclude that the baboon is a good animal model for the study of endometriosis.

The objective of this study was to test the hypothesis that ultrasound covers and sonographic gels, used during vaginal ultrasound, are toxic for mouse embryonic development in vitro. A prospective randomized design was used on pronucleate ova of F1 hybrid CBA x C57Bl female mice. The mice were superovulated with pregnant mare's serum gonadotrophin and human chorionic gonadotrophin and mated with CBA x C57Bl males. The pronucleate ova were randomly divided between culture media with the addition of commercially available ultrasound covers and sonographic gels in different concentrations. As controls and potential alternatives, plastic polyethylene bags and paraffin oil were tested simultaneously. Embryo-toxicity was assessed by documenting cleavage capacity, blastocyst formation and embryo degeneration in vitro. Exposure of culture medium to the ultrasound covers and sonographic gels tested resulted in a severely reduced cleavage capacity, a high incidence of embryo degeneration and absent or impaired blastocyst formation. This toxic effect could be reduced by high dilutions in vitro. In contrast, plastic polyethylene bags and paraffin oil had no influence on in-vitro development of mouse ova. We conclude that commercially available ultrasound latex covers and sonographic gels are toxic for mouse embryos and can potentially influence embryonic development during infertility treatment. It is safer to perform vaginal ultrasonic measurements using non-toxic paraffin oil (as contact fluid) and plastic polyethylene bags (as ultrasonic cover).

In women with endometriosis, changes in peripheral blood and peritoneal fluid white blood cell (WBC) populations have been reported, but it is known whether these alterations are casually related to or a consequence of endometriosis. The purpose of this study was to test the hypothesis that peripheral blood and peritoneal fluid WBC populations are altered in baboons with spontaneous and induced endometriosis compared to animals without disease. Peripheral blood and peritoneal fluid samples were obtained at laparoscopy from 60 baboons with a normal pelvis (n = 23), spontaneous endometriosis (n = 19) and induced disease (n = 12), luteal phase (n = 20), pregnancy or nursing (n = 11) and in non-cycling animals (n = 8). The WBC concentration was analysed with a Coulter counter and fluorescent antibody cell separation (FACS) analysis was used to measure cluster designation (CD)2, CD4, CD8, interleukin (IL)2R and leucine (Leu) M5 subsets. In peripheral blood, the percentage of CD4+ and IL2R+ cells was increased in baboons with stage II-IV spontaneous or induced endometriosis, suggesting that alterations in peripheral blood WBC populations may be an effect of endometriosis. In peritoneal fluid the WBC concentration and percentages of Leu M5+ macrophages and CD8+ lymphocytes were only increased in baboons with spontaneous endometriosis and not in animals with induced disease, suggesting that alterations in peritoneal fluid WBC populations may lead to the development of endometriosis. In summary, the results of this study suggest that peripheral blood and peritoneal fluid immune cell populations are affected in baboons with endometriosis.

This study was done to test the hypothesis that the incidence and recurrence of retrograde menstruation is higher in baboons with spontaneous endometriosis than in those without. A total of 399 laparoscopies was performed on 113 female baboons. Group 1 consisted of 84 animals with a normal pelvis (including 23 that later underwent induction of endometriosis and were assigned to group 4), group 2 comprised nine baboons with spontaneous endometriosis acquired during the last 2 years of the study, group 3 had 18 baboons with long-term spontaneous disease, and group 4 comprised 25 animals with induced endometriosis. Retrograde menstruation was defined by the presence of blood-stained peritoneal fluid (red or dark brown) during menses. Recurrence of retrograde menstruation was analysed during the first two laparoscopies in 13 baboons. Peritoneal fluid was 10 times more frequently blood-stained during menses (62%) than during non-menstrual phases (6%). Retrograde menstruation was observed more frequently in animals with spontaneous disease (groups 2 and 3, 83%) than in animals with a normal pelvis (group 1, 51%). Recurrence of retrograde menstruation was observed more frequently in baboons with spontaneous endometriosis (5/5) than in those without (3/8). The results of this study demonstrate that retrograde menstruation is common in baboons, with a higher prevalence and recurrence in animals with spontaneous endometriosis than in those without.

This study was performed to document for the first time peritoneal fluid volumes and steroid hormone levels in baboons with and without endometriosis. A laparoscopy was carried out in 19 female baboons (11 with a normal pelvis and 8 with histologically proven spontaneous minimal/mild endometriosis) during 64 cycles in the early luteal phase. Peritoneal fluid was measured and aspirated. The pelvis was examined for evidence of recent ovulation and endometriosis. Peritoneal fluid and serum were assayed for 17beta-estradiol and progesterone. The mean volume of peritoneal fluid and its concentration of 17beta-estradiol and progesterone were 2.6 ml, 679 pmol/l and 64 nmol/1, respectively. No differences were observed between animals with or without either endometriosis or luteinized unruptured follicle syndrome. The peritoneal fluid and serum steroid levels were comparable to those found in women. The results presented are similar to those obtained in women with endometriosis and this suggests that the baboon can be used for the study of this disease.

Objective: To examine the influence of depression levels and coping on IVF outcome in women, taking into account the cause of infertility.

This case report describes a couple suffering from infertility secondary to psychogenic anejaculation, which was refractory to all conservative treatment modalities. A first trial of microsurgical vas aspiration in combination with in-vitro fertilization (IVF) resulted in a pregnancy. After 2 years, three more trials of microsurgical vas aspiration in combination with either IVF or subzonal insemination (SUZI) resulted in embryo transfer without pregnancy. Finally, after 3 years, spermatozoa obtained by rectal probe stimulation under general anaesthesia were cryopreserved. A second intracytoplasmic sperm injection (ICSI) procedure using these cryopreserved spermatozoa also resulted in a second pregnancy. Although sperm concentration was in the normal range, in all samples obtained by either rectal probe electrostimulation or microsurgical vas aspiration, motility was <30% in all but two samples.

This case report describes a couple suffering from infertility secondary to psychogenic anejaculation, which was refractory to all conservative treatment modalities. A first trial of microsurgical vas aspiration in combination with in-vitro fertilization (IVF) resulted in a pregnancy. After 2 years, three more trials of microsurgical vas aspiration in combination with either IVF or subzonal insemination (SUZI) resulted in embryo transfer without pregnancy. Finally, after 3 years, spermatozoa obtained by rectal probe stimulation under general anaesthesia were cryopreserved. A second intracytoplasmic sperm injection (ICSI) procedure using these cryopreserved spermatozoa also resulted in a second pregnancy. Although sperm concentration was in the normal range, in all samples obtained by either rectal probe electrostimulation or microsurgical vas aspiration, motility was <30% in all but two samples.Keywords:electroejaculation/idiopathic anejaculation/microsurgical vas aspiration