In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in ...cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians.In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of "cancer and fertility preservation". A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation.Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sperm cryopreservation is a procedure widely used to store gametes for later use, to preserve fertility in patients prior to gonadotoxic treatments or surgery, and for sperm donation programs. The ...purpose of the study was to assess the impact of cryopreservation on human sperm transcriptome. Semen samples were collected from 13 normospermic men. Each sample was divided into two aliquots. The total RNA was immediately extracted from one aliquot. The second aliquot was frozen and total RNA was extracted after a week of storage in liquid nitrogen. The RNA samples were randomized in four pools, each of six donors, and analyzed by microarrays. The paired Significance Analysis of Microarray was performed. We found 219 lower abundant transcripts and 28 higher abundant transcripts in cryopreserved sperm than fresh sperm. The gene ontology analysis disclosed that cryopreservation alters transcripts of pathways important for fertility (i.e., spermatogenesis, sperm motility, mitochondria function, fertilization, calcium homeostasis, cell differentiation, and early embryo development), although the increase of some transcripts involved in immune response can compensate for the harmful effects of freezing.
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Background Healthy individuals and patients with cancer who are carriers of germline pathogenic variants in the BRCA1/2 genes face multiple reproductive challenges that require appropriate counseling ...and specific expertise. Main body On December 5th-7th, 2019, patient advocates and physicians with expertise in the field of reproductive medicine, fertility preservation, and oncology were invited to "San Giuseppe Moscati" Hospital in Avellino (Italy) for a workshop on reproductive management of women with germline pathogenic variants in the BRCA1/2 genes. From the discussion regarding the current evidence and future prospective in the field, eight main research questions were formulated and eight recommendations were developed regarding fertility, fertility preservation, preimplantation genetic testing, and pregnancy in healthy carriers and patients with cancer. Conclusion Several misconceptions about the topic persist among health care providers and patients often resulting in a discontinuous and suboptimal management. With the aim to offer patient-tailored counseling about reproductive issues, both awareness of current evidences and research should be promoted. Keywords: Fertility, BRCA, Preimplantation genetic testing, Oocyte cryopreservation, Ovarian reserve, Cancer
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in ...estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated.
Methods:
This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy endpoint was the number of retrieved mature Metaphase II (MII) oocytes. Secondary efficacy and safety endpoints were total number of oocytes, maturation rate, fertilization rate, number of cryopreserved embryos, peak estradiol levels, progesterone levels, and total gonadotropin dose. Data for each endpoint were reported and analyzed thorough mean ratio (MR) with 95% confidence interval (CI).
Results:
A total of 11 records were selected including 2,121 patients (990 patients underwent COS with letrozole and 1,131 COS without letrozole). The addition of letrozole to COS did not have any negative effect on the number of mature oocytes collected (MR = 1.00, 95% CI = 0.87–1.16;
P
= 0.967) and the other efficacy endpoints. COS with letrozole was associated with significantly decreased peak estradiol levels (MR = 0.28, 95% CI = 0.24–0.32;
P
< 0.001). Similar results were observed in the secondary analysis including only breast cancer patients.
Conclusions:
These findings are reassuring on the efficacy and safety of COS with gonadotropins and letrozole and are particularly important for fertility preservation in women with hormone-sensitive cancers.
Data on fertility after autologous hematopoietic stem cell transplantation (aHSCT) in women with multiple sclerosis (MS) are inconclusive. This study aims to report on post-aHSCT menstrual resumption ...in a multi-center MS-women cohort. Out of 43 women, 30 (70%) recovered menses after a mean time of 6.8 months. Older age (odds ratio (OR) = 0.5, p < 0.0001) and previous pulsed cyclophosphamide (OR = 0.44, p = 0.005) were independently associated with a reduced menstrual recovery probability. Conditioning regimens’ intensity resulted not associated with post-procedure amenorrhea. Our results highlight younger age as significantly associated with menses recovery; proper fertility counseling for MS women candidated to aHSCT both prior- and post-transplantation is therefore warranted.
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Offering ovarian function and/or fertility preservation strategies in premenopausal women with newly diagnosed breast cancer candidates to undergo chemotherapy is standard of care. However, few data ...are available on uptake and main reasons for refusing these options.
The PREFER study (NCT02895165) is an observational, prospective study enrolling premenopausal women with early breast cancer, aged between 18 and 45 years, candidates to receive (neo)adjuvant chemotherapy. Primary objective is to collect information on acceptance rates and reasons for refusal of the proposed strategies for ovarian function and/or fertility preservation available in Italy.
At the study coordinating center, 223 patients were recruited between November 2012 and December 2020. Median age was 38 years (range 24 - 45 years) with 159 patients (71.3%) diagnosed at ≤40 years. Temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) was accepted by 58 out of 64 (90.6%) patients aged 41-45 years and by 151 out of 159 (95.0%) of those aged ≤40 years. Among patients aged ≤40 years, 57 (35.8%) accepted to access the fertility unit to receive a complete oncofertility counseling and 29 (18.2%) accepted to undergo a cryopreservation technique. Main reasons for refusal were fear of delaying the initiation of antineoplastic treatments and contraindications to the procedure or lack of interest in future childbearing. Patients with hormone-receptor positive breast cancer had a tendency for a higher acceptance rates of ovarian function and/or fertility preservation strategies than those with hormone-receptor negative disease.
More than 90% of premenopausal women with early breast cancer, and particularly those with hormone receptor-positive disease, were concerned about the potential risk of chemotherapy-induced premature ovarian insufficiency and/or infertility and accepted GnRHa administration. Less than 1 out of 5 women aged ≤40 years accepted to undergo cryopreservation strategies.
Cancer treatments frequently impair the reproductive ability of patients by damaging spermatogenesis. International guidelines recommend semen cryopreservation to preserve the fertility of ...oncological adult males and pubertal boys. However, due to the low usage rate of banked samples, not a lot of data on assisted reproductive treatments (ART) success rates in this population and follow-up data for children born are available in the literature. The aims of this study were to report our 15 years of experience, the clinical outcomes of ART as well as neonatal characteristics of babies born. We retrospectively reviewed 682 oncological patients who were referred to our center from 2004 to 2019 for fertility preservation. Over the years, only 26 patients (4%) returned to use their sperm by ART. They were survivors of leukemia and lymphomas (52%), testicular cancer (20%), and other malignant diseases (28%). These couples performed 45 cycles: 34 intracytoplasmic sperm injection (ICSI) plus 11 frozen embryo transfers. A total of 13 children were born, with 35% of the cumulative live-birth delivery rate per couple. No stillbirths or malformations were recorded. These successful findings demonstrated that pregnancy could be safely achieved using frozen-thawed sperm of cancer survivors who cryopreserved before gonadotoxic therapies.
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The male reproductive system may be a potential target for SARS-CoV-2 since the presence of ACE and TMPRS2 receptors. After a first report of the presence of SARS-CoV-2 in semen of COVID-19 patients, ...several papers reported that SARS-CoV-2 was not detected in the semen. However, some evidences indicated that COVID-19 disease could impair semen parameters. During the infection, or in a short period after, a reduction in sperm concentration and motility and an increase in DNA fragmentation were observed, even in asymptomatic patients. There is no conclusive data exploring whether this damage changes with time. We investigated whether COVID-19 disease has a negative impact on semen parameters and male reproductive potential after recovery.
In this longitudinal retrospective study, we enrolled 20 men who had COVID-19 disease. We compared sperm parameters in samples collected before COVID-19 and after infection (8.3 ± 4.8 months). We also evaluated the reproductive potential in pre- and post-COVID-19 infertility treatments of 8 self-controlled couples as well as in 40 cycles after COVID-19 infection of the male partner.
For most patients, we obtained results of more than one semen analysis before and after COVID-19. After adjusting for age, days of sexual abstinence, frequency of ejaculations and presence of fever, we found no significant difference over time in any semen parameter. The interval between COVID-19 infection and subsequent infertility treatments was 10.7 ± 7.5 months. There were no differences in the embryological and clinical outcomes of infertility treatments performed before and after male infection. One couple obtained a single pregnancy in the post COVID-19 IUI. Normal fertilization (65%), cleavage (99%) and blastocyst development (40%) rates in treatments performed after male infection were within the expected range of competencies. A total of 5 singleton and 1 twin clinical pregnancies were obtained, and 6 healthy children were born. A total of 10 blastocysts have been cryopreserved.
Our data are reassuring that COVID-19 disease has no negative effect on semen quality and male reproductive potential when semen samples are collected three months or more after infection.
Fertility after bowel resection for endometriosis Ferrero, Simone, M.D; Anserini, Paola, M.D; Abbamonte, Luiza Helena, M.D ...
Fertility and sterility,
07/2009, Volume:
92, Issue:
1
Journal Article
Peer reviewed
Open access
Objective To determine the pregnancy rate after bowel resection for rectosigmoid endometriosis. Design Prospective cohort study. Setting University hospital. Patient(s) Forty-six symptomatic women ...with bowel endometriosis requiring colorectal resection. Intervention(s) Bowel resection by either laparoscopy or laparotomy. Main Outcome Measure(s) Pregnancy rate after surgery. Result(s) The pregnancy rate was higher in women who underwent bowel resection by laparoscopy (57.6%) than in those who underwent laparotomy (23.1%). No significant difference was observed in pregnancy rate and mode of conception between women with different fertility status before bowel resection. Women who conceived were significantly younger than those who did not conceive; only 26.7% of women aged ≥35 years conceived after bowel resection. Uterine adenomyosis was more frequently present in women who did not conceive than in those who conceived. Infertile women who conceived had a shorter length of infertility before surgery than those who did not conceive. Conclusion(s) Laparoscopic colorectal resection is less likely to impact negatively on fertility than the laparotomy approach. Previous laparotomies, age ≥35 years, uterine adenomyosis, and longer duration of infertility before surgery are associated with decreased pregnancy rate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In assisted reproduction technology embryo competence is routinely evaluated on morphological criteria but efficacy remains relatively low. Additional information could be obtained by evaluating ...pronuclear (PN) morphology. Up to now controversial results have been reported about the prognostic value of PN score. One of the main limitations of literature data is the use of different PN classification methods. In this regard, in 2011 the ESHRE and Alpha Scientists in Reproductive Medicine defined three PN categories to standardize zygote assessment. In this study we evaluated whether the consensus ESHRE-Alpha system for the pronuclear scoring could be an useful additional criterion to improve prediction of embryo implantation potential.
This is a retrospective, longitudinal, observational, cohort study. We included 3004 zygotes from 555 women who underwent ICSI treatment at our Center between January 2014 and June 2019. The PN were categorized as score 1: symmetrical, 2: non-symmetrical, 3: abnormal. A subset of 110 zygotes did not cleaved. On day 2-3 1163 embryos were transferred, 232 arrested, and 9 were cryopreserved. Among the 1490 embryos cultured up to day 5-7, 516 became blastocysts: 123 were transferred on day 5 and 393 were cryopreserved. Comparisons of age, cleavage and blastocyst rate, quality of embryos, implantation success among PN score groups were evaluated by chi-square test or Kruskal-Wallis test as appropriate. Potential predictors of embryo implantation were first tested in univariable analysis using generalized estimating equations taking into account correlation between embryos originated from the same patient. Then, variables potentially associated with implantation success (P<0.05) were included in a multivariable analysis for calculating the adjusted odds ratio (OR) and 95% confidence interval (CI).
There was no significant difference in patients'age, cleavage and blastulation rates, and embryo morphology among the three PNscore groups. The PN score 1-embryos had a greater implantation success respect to score 2-3-ones (OR 1.83; 95% CI 1.34-2.50, P=0.0001). Consistently, the pronuclear score remained predictive of implantation in top quality embryos (OR 1.68; 95%CI 1.17-2.42, P= 0.005).
The consensus pronuclear score may be routinely included among criteria for embryo evaluation to increase patients' chance of becoming pregnant.
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