Reproductive Medicine Specialists Research Articles

Best Practice Recommendations for Infertility Management.

The objective of this document is to provide guidance to the infertility specialist, gynecologist, embryologist, and counselors on the management of sub-fertility and brief them with the recent advances in the field. These recommendations will aid the aforementioned healthcare professionals in everyday clinical decisions about appropriate and effective care of their patients with the best available evidence. Extensive deliberations, discussion, and brainstorming was done between different reproductive medicine (RM) specialists, to develop the recommendations. A systematic review of the literature published up to June 2019 was carried out using PubMed and Cochrane Collaboration Library. International guidelines, cohort studies, case series, observational studies, and randomized controlled trials currently available in the literature were reviewed. Indian data whatever available was also reviewed. Primary meetings were held with leading reproductive medicine specialists. Each topic was brainstormed on by a group of reproductive medicine experts, who then prepared the first draft of the recommendation. These recommendations then were reviewed by Dr. Jaideep Malhotra, Dr. Gouri Devi, and Dr. Madhuri Patil along with the chief co-ordinator of each consensus to finalize the final draft. From the literature and discussion of the available evidence, several topics were identified for which evidence is inconsistent, insufficient, or non-existing. For the benefit of couples undergoing several treatments, the working committee recommends that future research, where possible in well-designed RCTs, will help in establishing evidence for a particular practice. In the Indian context, one also needs to take into consideration facilities and options available, cost, lack of insurance coverage, experimental nature of some advanced techniques used.

The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database.

A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal anti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibiotics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, 'unmasking', dataset analyses were carried out as well. Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications, which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed significant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7-20.3), 14.3 (9.1-22.4) and 58.7 (36.3-95.9). A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.

Relugolix combination therapy and symptoms of uterine myomatosis – selected case reports of indication spectrum and treatment outcomes

Summary: Objective: An illustrative review of the indications for relugolix combination therapy (RCT) in the management of symptoms associated with uterine myomatosis. Methods: A set of annotated case reports from outpatient and clinical practice. Results: The fi le includes a non-invasive methodology for defining excessive menstrual bleeding using the pictorial bleeding assessment chart (PBAC). It also presents the use of RCT as a fertility-sparing procedure prior to elective myomectomy and the management of isthmic fibroids as an uterine factor of infertility. Cases of RCT of adenomyosis in primary sterility and in extragenital forms of endometriosis are commented. Emergent events associated with complications of myomatosis in pregnancy are represented by a case report of necrotizing diff use myomatosis in puerperium. The differential-diagnostic confusion of adnexal pathology and myomatosis, RCT as a final solution to failed pharmacotherapy, and the alternative of hysterectomy in premenopause illustrate the diverse spectrum of indications for pharmacological treatment, including the possibility of dual therapy with RCT and aGnRH. Conclusion: Relugolix combination therapy as an effective and safe causal treatment expands the therapeutic spectrum and options for reproductive medicine specialists and registering gynaecologists. The availability of conservative treatment in combination with surgical treatment leads to optimalization and greater effectiveness of therapeutic procedures and increased quality of life for women with myomatosis. Key words: relugolix combination therapy – uterine fibroid symptoms

Optimizing the "Time to pregnancy" in women with multiple sclerosis: the OPTIMUS Delphi survey.

The debate on how to manage women affected by multiple sclerosis (MS) during reproductive age is still open, as is the issue of fertility in such patients. Main issue regard the identification of the optimal window for pregnancy and how to deal with medical therapy before and during conception. The aim of this Delphi consensus was to collect the opinions of a multidisciplinary group, involving reproductive medicine specialists and neurologists with experience in the management of multiple sclerosis women with reproductive desire. Four experts plus scientific coordinators developed a questionnaire distributed online to 10 neurologists and later discussed the responses and amended a list of statements. The statements were then distributed via an online survey to 23 neurologists (comprising the first 10), who voted on their level of agreement/disagreement with each statement. Consensus was achieved if agreement or disagreement with a statement exceeded 66%. Twenty-one statements reached consensus after two rounds of voting, leading to the following main recommendations: (1) Fertility evaluation should be suggested to wMS, in case of the need to shorten time to pregnancy and before treatment switch in women on DMTs contraindicated in pregnancy, particularly in case of highly active disease and age > 35 years. (2) ART should not be discouraged in wMS, but the use of DMTs until pregnancy confirmation should be suggested; ART may be considered in order to reduce time to pregnancy in MS women with a reduced ovarian reserve and/or age > 35 years, but in case of an expected poor ART prognosis and the need for more than one ART cycle, a switch to a high-efficacy DMD before ART should be offered. (3) Oocyte cryopreservation may be considered in women with reduced ovarian reserve, with unpredictable time to complete diagnostic workup and achieve disease control; a risk/cost-benefit analysis must be performed in women >35 years, considering the diminished ovarian reserve. This consensus will help MS neurologists to support family planning in wMS, respecting MS therapeutic needs while also taking into account the safety and impact of advancing age on fertility.

The silent world of assisted reproduction: A qualitative account of communication between doctors and patients undergoing in vitro fertilisation in Australia.

In vitro fertilisation (IVF) is now a common assisted reproductive technology (ART) procedure globally, with 8 million children alive today having been conceived utilising IVF. For many patients, IVF is a difficult experience with many discontinuing treatment because of emotional, relationship and financial stress,or intolerable physical side effects of hormone treatments. A qualitative study, in which 31professionals and 25patients from the ART sector in Australia were interviewed. The interviews were analysed using codebook thematic analysis. Our data indicates there are 'silences' within the therapeutic relationship of IVF, which may limit the capacity for patients to prepare emotionally, financially,or medically for the procedure, and may contribute to psychological distress and dissatisfaction with care. These 'silences' include what the patient 'is not told' by their clinician or 'does not hear' and what the patient feels they 'cannot say'. Drawing upon the work of Jay Katz, Charis Thompson,and Miles Little on 'silences' and performance in clinical practice, we argue that although IVF is a complex and multifaceted procedure that is often conducted in a commercial setting, the clinical and therapeutic relationship between doctor and patient remains pivotal to the experiences of patients. The 'silences' within this relationship may impact negatively on decision-making, and on the delivery and experience of care. Careful attention to the realities of IVF treatment in the clinic room (and awareness of the performances that hide them) should allow for more present and compassionate care. Such care may leave patients more satisfied with their experience and their choices, regardless of treatment outcomes. This article draws on interviews with patients who had undergone or were currently undergoing IVF, as well as a range of representatives from the ART community (including reproductive medicine specialists, general practitioners, fertility nurses, counsellors, administrators in ART businessesand embryologists).

Fertility-sparing surgery: a hopeful strategy for young women with cancer.

Fertility preservation in cancer patients is currently based on either assisted reproductive technology or fertility-sparing surgery. Loss of fertility may be caused by excisional surgery associated with an adnexal or uterine pathology or secondary to gonadal insufficiency caused by chemotherapy or radiation. The counseling of these patients is very important, being carried out jointly by the oncologist, gynecologist, and reproductive medicine specialist. Reproductive surgery usually requires avoiding laparotomy to significantly reduce the formation of adhesions and trauma or tissue damage. This is done using standard laparoscopic surgery or robotic surgery (computer-assisted laparoscopy), a method increasingly used and accessible to all specialists who want to maintain the fertility of their patients with various oncological diseases.

P-470 Prediction of the cumulative live birth rate of IVF using a human embryonic stem cells-derived trophoblastic spheroid implantation model

Abstract Study question Can the attachment rate of a human embryonic stem cell-derived trophoblastic spheroids (BAP-EB) onto endometrial epithelial cells predict the cumulative live birth rate of an IVF cycle? Summary answer The BAP-EB attachment rate offers modest prediction of the cumulative live birth rate of women aged ≥35 years undergoing IVF. What is known already Implantation failure is one of the major causes leading to a low IVF success. There is no reliable tool for assessing endometrial receptivity in IVF. Study design, size, duration Prospective observational study of 240 infertile women from 2017 to 2021. Participants/materials, setting, methods Infertile women with regular cycles attending IVF centres were recruited. Endometrial aspirates were collected from a natural cycle one month before IVF for the BAP-EB attachment rate. The cumulative live birth rate of a stimulated cycle and its derived frozen embryo transfer cycles within 6 months of ovarian stimulation were obtained. Main results and the role of chance The BAP-EB attachment rate in women with a cumulative live birth was similar to those who failed to have a live birth. When women were stratified by age into <35 years and ³35 years, the BAP-EB attachment rate was significantly higher only in women aged ³35 years who had a live birth when compared to those without a live birth. The receiver operating characteristic (ROC) curve analysis of BAP-EB attachment rate in predicting cumulative live birth showed the area under the curve (AUC) of 0.559 (95% CI 0.479 – 0.639, p = 0.151), 0.448 (95% CI 0.310 – 0.585, p = 0.461) and 0.613 (95% CI 0.517 – 0.710, p = 0.026) for all ages, age <35 and ≥35 respectively. Limitations, reasons for caution BAP-EB and the isolated endometrial epithelial cells may not fully represent the in vivo developed human blastocysts and endometrial cells, respectively. The in vitro nature of the experiments and the limited sample size in this study may also limit the interpretation of the data. Wider implications of the findings Implantation failure is one of the major reasons contributing to the low success rate of IVF. The BAP-EB-endometrium attachment assay could potentially be used by reproductive medicine specialists to better counsel the couples who fail in IVF treatment. Trial registration number NCT02713854

Ovarian reserve is influenced by ethnicity – a fact, a reproductive medicine specialist should be aware of

Ovarian reserve is influenced by ethnicity – a fact, a reproductive medicine specialist should be aware of

(335) Unconsummated Marriage: Findings and Outcomes of Ccouples Visiting an Andrology Clinic

Abstract Introduction Failure to have a penetrative peno-vaginal intercourse among the heterosexual married couples is termed as unconsummated marriage (UCM). Unheard in most western countries, UM is often seen in culturally conservative countries like India where majority still don't have sexual encounters prior to marriage. Nonconsummation is most commonly due to erectile dysfunction (ED, vaginismus or forced marriage. The management requires an aggressive early treatment otherwise some even end up in divorce. Objective To report the clinical characteristics and outcomes of males visiting Andrology clinic seeking treatment for UCM Methods This is a retrospective study of 62 male patients seeking treatment for UCM who presented to the andrology clinic from Jan 2018 to May 2022. All were subjected through detailed clinical history including patient demographics, physical examination and necessary investigations. Wherever possible, the female partner was also involved for discussion and if found abnormal during clinical history was referred to the female reproductive medicine specialists. Results Of the 62 male patients, majority (56, 90%) complained erectile dysfunction as the cause for UCM. Other causes being lack of anatomical knowledge of intercourse (2/62), vaginal pain while attempting penetration (4/62), performance anxiety (5/62) and forced marriage (4/62). There was overlap of more than 1 cause in few patients. The mean duration of UCM was 12.6 months (range 2-128 months). Of the 62 patients, 13 had master’s degree and 42 had bachelor’s degree. Among the 56 patients with ED, 22/56 had already received sildenafil or/and tadalafil from primary care physician with no success. Dual therapy (simultaneous on-demand sildenafil and daily tadalafil) helped 23/56 males to consummate their marriage. Six males didn’t come for follow-up after 2 visits and even refused to answer our questions on phone. Two males did not seek any further treatment for ED after oral medications failed and proceeded with assisted reproductive techniques to conceive for social reasons. Of the four females with vaginismus, 3 successfully consummated following vaginal dilator therapy and psychosexual counselling, but the remaining 1 proceeded with intrauterine insemination to conceive. Consummation was achieved in 6 men who received intra-cavernosal injection of reconstituted 20mcg alprostadil. Three men consummated following penile prosthesis placement (2 semirigid and 1 inflatable). Two couples divorced as the wives wanted “natural” erections from their husbands and not “medicated” erections. Three couples were in the process of divorce. Twelve of the 62 men were accompanied by their parents or in-laws in their first or second clinical visit. Conclusions As against the usual assumption, UCM is commonly seen even among the well-educated class. UCM should be considered as an andrological emergency and timely intervention is required to prevent termination of marriage. When oral medications and counselling doesn’t work, do not hesitate to start on intra-cavernosal injections and occasionally may be a penile implant surgery. Due to social and familial concerns, few may decide to seek assisted reproductive techniques to conceive without sexual intercourse and the same may be considered. Disclosure No

Expert consensus on the morphological evaluation of human cleavage-stage embryos and blastocysts.

Introduction To date, conventional morphological indicators of embryos are still used as the primary rating parameters or criteria. However, standardized and easy-to-use morphological evaluation criteria for human cleavage-stage embryos and blastocysts remain lacking. According to the Istanbul Consensus,[1] morphological scoring systems for cleavage-stage embryos, trophectoderm (TE) cells, and inner cell mass (ICM) include three ratings, namely good, fair, and poor. However, the criteria are straightforward and less detailed, which increases the subjectivity of the embryo evaluation procedure. In this consensus, we provide a scoring system for cleavage-stage embryos and blastocysts in which the evaluative indicators are explained using illustrative images. In addition, this consensus quantifies a variety of evaluative indicators, such as the number of cells in cleavage-stage embryos and the number of TE and ICM cells in blastocysts, thereby improving the operability in practice. Simultaneously, it refines the grade of embryo assessment, defines high-quality and usable embryos, and displays abnormal morphological characteristics of embryos, which facilitates the selection of embryos for transfer. This consensus was initiated by the Chinese Association of Reproductive Medicine and compiled jointly by European and Oceanian embryologists in an effort to further optimize the quality management systems of assisted reproduction laboratories and enhance the performance of assisted reproduction technology. Consensus Points Morphological indicators for cleavage-stage embryos The number of blastomeres, degree of fragmentation, cell size, and multinucleation profile of the embryo are the main morphological indicators for scoring cleavage-stage embryos.[2] Cell numbers The number of blastomeres signifies the developmental rate of the embryo and is considered the most important indicator of embryo scoring.[3] Generally, high-quality cleavage-stage embryos exhibit the appropriate developmental kinetics and synchrony of division. Fragmentation Embryo fragmentation is strongly associated with pregnancy outcomes.[4] The degree of fragmentation is usually expressed as the percentage of fragmented blastomeres in the total embryo volume, with <10% being preferable. When larger fragments are indistinguishable from blastomeres, a round cytoplasm diameter of <45 μm on day 2 or <40 μm on day 3 is the recommended definition of a fragment [Supplementary Figure 1, https://links.lww.com/CM9/B448].[5] Symmetry Theoretically, embryonic mitosis produces daughter cells of equal sizes. Embryos with even cleavage have shown lower rates of multinucleation and aneuploidy, as well as a significantly elevated implantation rate. However, the symmetry and size of all blastomeres also depend on the developmental pattern and specific stage of the embryo, namely the stage-specific cleavage pattern [Supplementary Table 1, https://links.lww.com/CM9/B449].[6] Multinucleation An embryo is considered multinucleated if more than one nucleus is present in one or more blastomeres. However, the smaller size, larger number, and overlapping of embryonic blastomeres on day 3 would considerably increase the difficulty of observation. Therefore, for day-3 embryos, where multinucleation is difficult to observe, incorporating the observation results of multinucleation on day 2 for embryo scoring is possible. Scoring criteria for cleavage-stage embryos Day-2 embryos The scoring criteria for cleavage-stage embryos on day 2 are presented in Supplementary Table 2, https://links.lww.com/CM9/B449. The superiority hierarchy of grades I, IIa, IIb, III, and IV embryos descends sequentially. Day-3 embryos The scoring criteria for cleavage-stage embryos on day 3 are presented in Supplementary Table 3, https://links.lww.com/CM9/B449 and Supplementary Figure 2, https://links.lww.com/CM9/B448. The following points should be noted: (i) Grade I embryos should be 8-cell embryos (day 3) developing from 4-cell embryos (day 2), and these 4-cell embryos have no multinucleation phenomenon. Grade I embryos should also be characterized by clear homogeneous cytoplasm (no vacuolation), tight intercellular junctions, and normal zona pellucida (no darkening, excessive thickness/thinness, abnormal shape, etc). However, the impacts of several abnormal morphological features on embryo development lack robust data support; therefore, these are not included as main scoring indicators. Embryos with any of the abnormal morphological features cannot be assessed as grade I or considered as the preferred choice [Supplementary Figure 3, https://links.lww.com/CM9/B448]; (ii) Relatively even cells are represented by the following equation: (large cell diameter–small cell diameter) / large cell diameter × 100% < 20%;[7] (iii) The superiority hierarchy of grade I, IIa, IIb, IIIa, IIIb, and IV embryos descends sequentially. Scoring criteria for blastocysts Blastocyst culture is an effective means for enabling embryo preference and selective single-embryo transfer. Therefore, refining the morphological scoring system for blastocysts is particularly important for accurately assessing their developmental potential. This consensus is based on the Gardner and Schoolcraft blastocyst scoring system,[8] combined with the Consensus on Human in Vitro Fertilization and Embryo Transfer Laboratory Manipulation (2016) developed by Chinese experts.[9] It divides the grading of embryos into six stages according to the expansion and hatching status of the blastocyst and adds a grade D to evaluate ICM cells [Supplementary Tables 4–6, https://links.lww.com/CM9/B449, Supplementary Figure 4, https://links.lww.com/CM9/B448]. Timing of observation Referring to the Istanbul Consensus[1], the time points for embryo observation were 44 ± 1 h and 68 ± 1 h after insemination for cleavage-stage embryos on days 2 and 3, respectively, and 116 ± 2 h, 140 ± 2 h, and 164 ± 2 h after insemination for blastocysts on days 5, 6, and 7, respectively. Each center may rationally modulate the timetable for embryo observation according to the characteristics of embryo development and working schedules; however, they should ensure consistency in the daily observation time. Recording methods Cleavage-stage embryos The following is the suggested format for writing cleavage-stage embryo grading: cell number and grade (eg, I/8 or 8I). Since the cell number is the most important indicator for embryo scoring, it is integrated into the grading criteria of this consensus and is also reflected in the writing format. Notably, not all embryos have visible blastomere nuclei (either mono- or multinucleated) on day 3. The clear presence of mononucleated blastomeres in the embryo and the proportion of mononucleated blastomeres to total blastomeres may be positively correlated with the developmental potential of the embryo and live birth rates. Therefore, this phenomenon can be recorded specifically. To report this, N indicates mononucleated blastomeres, MN indicates multinucleated blastomeres, and a number indicates the number of mono- or multinucleated blastomeres observed. Furthermore, blastomeres without nuclei are not recorded. For example, an 8-cell grade I embryo with six blastomeres observed as mononucleated is recorded as I/86N. Moreover, a 6-cell grade III embryo with one blastomere observed as multinucleated is recorded as III/61MN. This labeling approach may help improve the preferential selection of embryos. However, the presence and number of visible mononucleated blastomeres are not the main reference indicators for embryo assessment. Blastocysts The writing format for blastocyst grading is relatively consistent, and the scoring system can be further refined by adding a “+” or “−” to the TE and ICM grades, for example, 4B+A and 4BB−. This annotation approach may facilitate the preferential selection of embryos at additional levels; however, it is not used as an inter-laboratory embryo quality control criterion. Definition of high-quality embryos and blastocysts Cleavage-stage embryos Based on the Vienna Consensus[10] combined with the practical experience of multiple centers, this consensus recommends redefining high-quality embryos and usable embryos at the cleavage stage, as shown in Supplementary Table 7, https://links.lww.com/CM9/B449. All usable embryos can be used for embryo transfer, cryopreservation, or blastocyst culture. The grade I/8 (Day 3) embryos without fragments, developed from I/4 (Day 2) embryos, are defined as optimal embryos and are preferred for transfer. The early compaction of embryos on day 3 is a common phenomenon [Supplementary Figure 5, https://links.lww.com/CM9/B448]. With reference to relevant research combined with the practical experience of multiple centers, this consensus recommends the early compaction of embryos with ≥7 cells and the percentage of fragments <10% to be summarized as high-quality embryos. Additionally, blastocyst culture is recommended for grade IIIb embryos (Day 3), while grade-IV embryos should be discarded and are not recommended for embryo transfer or cryopreservation. Blastocysts Based on the Gardner and Schoolcraft blastocyst scoring system[8] combined with the practical experience of multiple centers, this consensus recommends redefining high-quality blastocysts and usable blastocysts, as shown in Supplementary Table 8, https://links.lww.com/CM9/B449. All usable blastocysts can be used for embryo transfer or cryopreservation. The following points are noteworthy: (i) Stage 3 and above low-quality blastocysts graded as CC on day 5/6 could be transferred, cryopreserved, or discarded, depending on the patient's condition and the low-quality blastocyst application strategy of each center; (ii) Early blastocysts that remain at stages 1 or 2 on day 6 are recommended to be cultured until day 7. By this time, if the cells exhibit good refractive properties, no large degenerative foci, and can reach stage 4 and above with a grade of AA, AB, BA, or BB, they can be used for embryo transfer or cryopreservation; (iii) This consensus adds a grade D for ICM to the conventional Gardner blastocyst scoring system, which aims to refine the conventional grade C for ICM. Blastocysts with an ICM grade D, as defined in this consensus, should be discarded to reduce the unnecessary financial burden on patients and the workload of laboratory personnel. Conclusion In this consensus, we provide a scoring system for cleavage-stage embryos and blastocysts in wherein the evaluative indicators are explained using illustrative images. It is our hope that these “consensus values” will form a common language for embryologists worldwide to further optimize the quality management systems of assisted reproduction laboratories and improve the performance of assisted reproduction technology. Conflicts of interest None. These guidelines are a reference for reproductive medicine specialists in clinical practice. The Chinese Association of Reproductive Medicine assumes no responsibility for results involving the inappropriate application of these guidelines and reserves the right to interpret and revise the guidelines.

Obstetrical outcomes of pregnant women 50 years and older compared to those aged 45-49 years: A systematic review and meta-analysis.

In this review, We compared clinical characteristics of pregnant women aged 50 and older with those aged 45-49. Pregnant women ≥45 years are strongly associated with pregnancy-related complications, such as cesarean section rate, gestational hypertension, gestational diabetes mellitus, and preterm birth. Although pregnant women ≥50 years are considered more high-risk, differences in pregnancy outcomes between those over 45 and 50 years of age are unclear. Our source strategy included using PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science databases to include studies published between January 1, 2010 and September 30, 2022. The study population was pregnant women 50 years and older; the control group was pregnant women aged 45-49 years. Primary outcomes were cesarean section, gestational hypertension, gestational diabetes mellitus, and preterm birth. The secondary outcomes were small-for-gestational age, 5-min Apgar score < 7, neonatal intensive care unit admission (as neonatal outcomes), nulliparity, assisted reproductive technology (ART), and multifetal pregnancy (as maternal backgrounds). The incidence of cesarean section, gestational hypertension, and preterm delivery was significantly higher in those 50 years and older; however, significant differences disappeared when pooled analyses were limited to singleton pregnancies. ART was significantly more likely to be used for conception of pregnant women ≥50 years. Infants of women ≥50 years were more likely to be admitted to NICUs. The differences in outcomes between the two groups are obviously influenced by multiple pregnancies, therefore, reproductive medicine specialists should aim for singleton pregnancies in ART.

Long-Term Fertility Function Sequelae in Young Male Cancer Survivors.

With advances in cancer treatment, such as cytotoxic chemotherapy and radiotherapy, grave new sequelae of treatment have emerged for young cancer survivors. One sequela that cannot be overlooked is male infertility, with reportedly 15% to 30% of cancer survivors losing their fertility potential. Cytotoxic therapy influences spermatogenesis at least temporarily, and in some cases, permanently. The degree of spermatogenesis impairment depends on the combination of drugs used, their cumulative dose, and the level of radiation. The American Society of Clinical Oncology has created an index to classify the risks to fertility based on treatment. Medical professionals currently use this risk classification in fertility preservation (FP) programs. FP programs are currently being promoted to prevent spermatogenesis failure resulting from cancer treatment. For patients who are able to ejaculate and whose semen contains sperm, the semen (sperm) is cryopreserved. Moreover, for patients who lack the ability to ejaculate, those with azoospermia or severe oligozoospermia, and those who have not attained puberty (i.e., spermatogenesis has not begun), testicular biopsy is performed to collect the sperm or germ cells and cryopreserve them. This method of culturing germ cells to differentiate the sperm has been successful in some animal models, but not in humans. FP has recently gained popularity; however, some oncologists and medical professionals involved in cancer treatment still lack adequate knowledge of these procedures. This hinders the dissemination of information to patients and the execution of FP. Information sharing and collaboration between reproductive medicine specialists and oncologists is extremely important for the development of FP. In Japan, the network of clinics and hospitals that support FP is expanding across prefectures.

Клинический случай диагностики и комплексного лечения наружного генитального эндометриоза у пациентки с бесплодием

The purpose of the article: to present a clinical case of diagnosis and complex treatment of endometriosis in a patient with infertility. Key points: the problem of infertility associated with endometriosis is extremely relevant. An important direction is the search for the most effective non-invasive method for diagnosing endometriosis, because performing laparoscopy only for diagnostic purposes leads to an increase in the number of unnecessary surgical interventions. The formation of a unified management strategy for patients with endometriosis is another task that reproductive medicine specialists face. Treatment of infertility and pain in endometriosis cannot always be carried out simultaneously. Conclusion. Magnetic resonance imaging (MRI) can be a key method of non-invasive diagnosis of endometriosis. An integrated approach to the treatment of infertility and endometriosis allows to determine the tactics, stop the pain syndrome, and achieve the desired pregnancy. Key words: clinical case, endometriosis, infertility treatment, reproductive medicine, ART.

Freezing techniques as fertility preservation strategies: a narrative review

Advances in the development of new chemotherapy and radiotherapy regimens have significantly improved the survival of cancer patients but many of these treatments have detrimental effects on gonadal function. These treatments may cause premature ovarian failure in females and azoospermia in males. Non-oncological conditions may also require therapies that put women's and men´s reproductive potential at risk. Moreover, an increasing number of women today decide to postpone maternity beyond the age of 35 due to social reasons with a possible affectation of future fertility due to the effect of age. The development and evolution of assisted reproductive techniques offer these patients new alternatives to preserve their fertility. The objective of this review is to describe the different options of fertility preservation. Oocyte vitrification for female and sperm banking for male are the first line for fertility preservation at the present time. Other techniques such as ovarian and testis tissue preservation, in vitro maturation of gametes, pharmacological protection (GnRH agonists and antiapoptotic agents) and surgical treatments (oophoropexy, selective radical trachelectomy) will be described. One of the most important steps in optimizing the results of these fertility preservation procedures in cancer patients is the need for prompt and timely referral to reproductive medicine specialists. Fertility preservation should be integrated as part of the oncological healthcare. Optimal counselling from healthcare professionals should always be present.

Fertility preservation counselling for women with endometriosis: a European online survey.

Endometriosis is a common cause for infertility. Decreased ovarian reserve due to pathology or surgical management can reduce the chances of natural pregnancy and limit the effectiveness of controlled ovarian stimulation during fertility treatment. Cryopreservation of oocytes or ovarian cortex prior to surgery or before loss of follicular capital is a strategy to preserve fecundity. An online survey was sent to reproductive specialists and gynecological surgeons representing major centers of reproductive medicine in Europe to investigate current fertility preservation practices for endometriosis patients. Of 58 responses, 45 (77.6%) in 11/13 countries reported the existence of endometriosis management guidelines, of which 37/45 (82.2%) included treatment recommendations for infertile patients. Most centers (51.7%) reserved fertility counselling for severe endometriosis (large endometriomas with or without deep endometriosis) while 15.5% of centers did not offer fertility preservation for endometriosis. To address non-uniformity in available guidelines and the diversity in fertility preservation practices, we propose an algorithm for managing patients with severe endometriosis most likely to be impacted by reduced ovarian reserve. Improved awareness about the possibilities of fertility preservation and clear communication between gynaecological surgeons and reproductive medicine specialists is mandatory to address the unmet clinical need of preventing infertility in women with endometriosis.

The management of haemoglobinopathies in pregnancy and childbirth

Key Content The haemoglobinopathies encompass a complex collection of red blood cell disorders that are responsible for considerable morbidity and mortality in women and their unborn children. Sickle cell disease and the thalassaemias are the commonest haemoglobinopathies encountered in UK clinical practice. A consistent standard of care will enable women with haemoglobinopathies to have a pregnancy that is as safe as possible, with good outcomes and minimal long‐term effects on their health and the health of their babies. The most effective way to deliver a consistent standard of care for these women is via the multidisciplinary team (MDT). The MDT should include a haematologist, cardiologist, maternal medicine obstetrician, specialist midwife, reproductive medicine specialist and a nurse specialist. The care of these women, within the MDT, should start with pre‐conception advice and continue through their antenatal care, intrapartum support and finally, provide postnatal considerations including contraception advice. Learning Objectives To understand the inheritance, incidence, detection and pathophysiology of the commonest haemoglobinopathies. To appreciate the role of pre‐conception advice and prenatal diagnosis in the management of women with a haemoglobinopathy. To appreciate the multidisciplinary team approach in managing women with these conditions. Ethical Issues Prenatal diagnostic techniques can be used to diagnose an affected pregnancy; however, diagnosis after conception means families must address the option of terminating the pregnancy. This requires expert counselling to minimise long‐term sequelae. The definitive prenatal tests – chorionic villus sampling and amniocentesis – are both associated with a small risk of miscarriage. Non‐invasive free fetal DNA (ffDNA) tests that will minimise the risk of testing to the developing fetus are being developed, but use of these tests will still require expert counselling both before and after a test is taken.

Reproductive Issues in Long-Term Surviving Patients following Therapy for Hodgkin's Disease in the Republic of North Macedonia: Risks of Infertility According to First-Line Treatment Regimens.

Infertility as a consequence of therapy presents a high psychosocial burden for HL patients. In the cohort of our analyzed patients, within the post-ABVD surviving patients, alterations of the spermogram were documented in a total of 6.1% of the male patients and 5.4% of the female patients developed amenorrhea. On the other hand, within the subgroup of surviving patients following BEACOPP chemotherapy, 60% of the male patients manifested defects in their spermogram, and as high as 28.6% of the female survivors reported loss of their monthly cycle. It has been reported on several occasions that even prior to treatment, the sperm of HL patients manifests poorer quality characteristics when analyzed against control specimens from healthy male donors. The analyzed results in ABVD-treated male HL patients confirm ABVD to be a safe regimen for males of all age categories, as well as for female patients under the age of thirty. In women above the age of 30, the infertility risk rate is relatively low (14%), which leaves the decision of preserving fertility to themselves. For all BEACOPP-treated female, as well as male patients, a consult with a reproductive medicine specialist is warranted prior to therapy, due to the high infertility risk, and the final decision should be made on an individual basis.

Practices, Attitudes, and Knowledge Among Healthcare Providers and Oncologists in China Regarding Male Fertility Preservation.

ObjectiveThe purpose of this study was to help to promote a better understanding of the male fertility preservation status in China.MethodsIn this cross-sectional survey, 1,912 healthcare providers and oncologists were surveyed anonymously using 16 questions carried out at community oncology practices in China from September 2018 to April 2021. 16 questions were designed to evaluate their knowledge on male fertility preservation in cancer patients, assess the factors they considered when deciding whether to discuss male fertility preservation with their patients.ResultsAmong the 1,912 healthcare providers (42.2% male), 1,713 (89.6%) considered that patients with cancer should be recommended for fertility preservation. 1,264 (66.1%) respondents were aware of male fertility preservation, but only 248 (13.0%) respondents knew the correct institutions. Whether a healthcare provide recommended fertility preservation to their patients depended on the provider's educational background, professional qualifications, hospital grade, area, department, and age. Among the healthcare providers, the three main factors for not recommending fertility preservation for patients with cancer were lack of suitability of the patient for fertility (28.2%), lack of knowledge of fertility preservation (28.6%), and lack of knowledge concerning the institutes that provide fertility preservation (25.4%).ConclusionDespite this, healthcare providers and oncologists in China showed a positive attitude toward fertility preservation in patients with cancer. Hence, the education of physicians should include fertility preservation, with the aim of increasing their knowledge and awareness. There should be more collaboration between oncologists and reproductive medicine specialists.

The changing world of IVF: the pros and cons of new business models offering assisted reproductive technologies

This analysis contrasts traditional not-for-profit academic with new corporate practices of reproductive medicine and offers an assessment of risks to quality of patient care with investors entering the for-profit reproductive medicine market. Large corporate enterprises may have a global impact on access to care while at the same time is putting at risk the training of the next generation of reproductive medicine specialists.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2

The Japan Society of Clinical Oncology (JSCO) published the “JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients” in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.