霍奇金淋巴瘤女性患者生殖能力

… Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if …

… In conclusion, we found no evidence of significant impairment in the fertility of female HL … out more subtle injury to ovarian function impairing female fertility among these survivors. …

… Therefore, we analyzed gonadal function and fertility. … However, 2 + 2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time. …

Key Points • The number of pregnancies in young women after ABVD treatment for HL is similar to that of controls.• In addition, 81% of patients who wished to become pregnant after ABVD had at least 1 birth.

… To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we …

… fertility status was related to age and chemotherapy regimen. Regarding sexuality, 14 (39%) of the female Hodgkin lymphoma … assess the perceived fertility status of female HL survivors. …

Simple Summary Hodgkin lymphoma (HL) mainly affects people during their reproductive years, making fertility an important part of survivorship. Although cure rates are high, chemotherapy can impair gonadal function, with the extent of damage depending on the specific regimens used, as well as on age and sex. To provide clearer, evidence-based counselling, we systematically reviewed studies published since 2000 and combined data from more than 7000 patients. Overall, the likelihood of presumed infertility after treatment was approximately 21% in adult women and 45% in adult men. Infertility risk varies widely by regimen: it is low after ABVD but substantially higher after regimens containing alkylating agents. Men are generally at greater risk than women, and boys treated during childhood/adolescence show particularly high vulnerability. These findings highlight the importance of personalized fertility counselling and help determine when fertility preservation before treatment is essential and careful post-treatment assessment may be sufficient.

… survivors indicated a good relative fertility in women and more fertility deficits in men.Fewer … , we decided to analyze female fertility retrospectively in lymphomas of long-term survivors …

… Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH …

The risk of premature ovarian insufficiency (POI) after Hodgkin's lymphoma depends on female age, type, and dose of gonadotoxic treatment. Treatment with ABVD rarely results in POI and impaired fertility, whereas treatment with BEACOPP or stem cell transplantation is associated with higher risks of ovarian failure. Reports on parenthood rates are reassuring, although some studies report reduced fertility after treatment. In this study, we evaluate the reproductive outcomes after Hodgkin's lymphoma and the risk of POI after different types of chemotherapy. This cohort study was conducted at the Fertility Clinic at Rigshospitalet University Hospital, Copenhagen, Denmark. Data was collected retrospectively from medical records from 1999 to 2020 and prospectively from 2020 to 2023. We included all female patients with Hodgkin's lymphoma, referred for fertility preservation between 1999 and 2022. End of follow‐up was December 31, 2023. Information about diagnoses, gonadotoxic treatment, and gynecologic and obstetric history was retrieved from medical records. A total of 59 women were included: 21 received low‐dose, 15 moderate‐dose, and 20 high‐dose chemotherapy (3 unknown). Ovarian tissue cryopreservation (OTC) was done for fertility preservation in 86%. Mean age at diagnosis was 23.9 (SD 4.9) years. While no women developed POI after low‐dose chemotherapy, 4 (27%) did after moderate‐dose and 10 (50%) after high‐dose chemotherapy. Among 38 women with a pregnancy wish, 30 achieved at least one livebirth after cancer. Mean age at first pregnancy was 29.7 (SD 4.0) years. The chance of delivery after high dose was lower compared with low‐dose chemotherapy (OR 0.06, 95% CI:0.01–0.68) ( p  = 0.020). Among 33 women with OTC, 21 achieved pregnancy and delivery without ovarian tissue transplantation (OTT). Nine women underwent OTT of whom four delivered (44%) a total of five children. The likelihood of livebirth and risk of POI depended on the type of chemotherapy, with the least number of deliveries and the highest risk of POI after high‐dose chemotherapy. Pregnancy rates were reassuringly high even among women with a single ovary after OTC, with only 20% returning for OTT. Our findings support that fertility preservation in Hodgkin's lymphoma patients should primarily be offered to those receiving moderate‐ to high‐dose chemotherapy.

… consideration future fertility in young women with breast cancer and Hodgkin’s lymphoma [HL] … in 99 women treated for Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 2012;84:755–61 …

… -with-hodgkin-lymphoma-or-non-hodgkin-lymphoma Survival rates of patients suffering from Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (… , reduced fertility and even infertility. …

Summary Background Adverse effects on reproductive function are a key concern in young women treated with chemotherapy for advanced Hodgkin's lymphoma. We aimed to identify risk factors for the extent of ovarian damage in women with Hodgkin's lymphoma treated with different chemotherapy regimens to inform accurate advice on options for fertility preservation. Methods We recruited female participants from the randomised phase 3 RATHL trial, aged 18–45 years, based on availability of participants at recruiting sites in the UK. The RATHL trial key inclusion criteria were histologically confirmed classic Hodgkin's lymphoma, stage IIB–IV or IIA with adverse features (bulky disease or more than two sites of involvement), no previous treatments, and a performance status of 0–3. As part of RATHL, participants were treated with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or AVD followed by an interim PET-CT scan. Participants who had negative interim scans (PET score of 1 to 3 according to the Lugano classification) were randomly assigned (1:1) by use of minimisation, stratified by interim PET score and study centre, to continue ABVD or AVD for four more cycles. Participants with positive scans (PET score of 4 or 5) were escalated to treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP-14 or escalated BEACOPP) for four cycles. For the protocol-driven prospective cohort substudy, ovarian function was assessed before treatment, during chemotherapy, and then annually for 3 years by use of serum antimüllerian hormone and follicle-stimulating hormone measurements. The RATHL study is registered with ClinicalTrials.gov, number NCT00678327. Findings Between Dec 13, 2010, and Dec 19, 2012, 67 eligible participants were recruited for this prospective cohort study; 57 had received ABVD or AVD (ABVD-AVD group) and ten BEACOPP-14 or escalated BEACOPP (BEACOPP group). Follow-up was fixed at 3 years. Antimüllerian hormone concentrations decreased during both chemotherapy regimens. At 1 year after chemotherapy, antimüllerian hormone concentrations recovered to a median of 10·5 pmol/L (IQR 4·3–17·3) in the ABVD-AVD group, but little recovery was seen after BEACOPP (median 0·11 pmol/L [0·07–0·20]). Age also affected the extent of ovarian function recovery, with antimüllerian hormone recovery in participants aged 35 years or older in the ABVD-AVD group to 37% (SD 10) of their before treatment concentrations, compared with full recovery to 127% (SD 12) in those younger than 35 years (p<0·0001). Follicle-stimulating hormone recovery to less than 25 IU/L occurred for 95% of women younger than 35 years in the ABVD-AVD group by 2 years and was also dependent on age (hazard ratio 0·49, 95% CI 0·37–0·65; p<0·0001). Interpretation Reduced recovery of ovarian function observed in women older than 35 years treated with ABVD or AVD compared with younger women indicates that treatment could reduce their reproductive lifespan and supports discussion of fertility preservation before treatment. Women treated with BEACOPP should be informed of its potential high gonadotoxicity. These findings warrant further investigation in large, prospective studies with fertility and reproductive lifespan as outcomes. Funding Medical Research Foundation and Cancer Research UK.

… on ovarian function in patients with Hodgkin's lymphoma (HL) … Ovarian functions of control group were evaluated while new … The degree of damage to ovarian function has also been …

… All patients were treated during the period from 1996 to 2002 for Hodgkin's lymphoma. This study has been carried out in accordance with the ethical standards of the responsible …

Abstract BACKGROUND Owing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment. OBJECTIVE AND RATIONALE The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors. SEARCH METHODS PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged <25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually. OUTCOMES After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6–34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55–59%; median 57%; two studies. elevated FSH 17–100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33–100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0–100%; median 51.5%; 26 studies. low inhibin B 19–50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0–57%, median 17%; 21 studies and low testosterone 0–43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH<p10 9%; one study and Males: azoospermia 0–50%; median 10%; six studies). Reports on chance to achieve pregnancy during survivorship are reassuring, although studies had their limitations and the results are difficult to evaluate. In the end, a diminished ovarian reserve does not exclude the chance of a live birth, and males with aberrant markers may still be able to conceive. WIDER IMPLICATIONS This review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.

We reviewed the effect of ovarian transposition (OT) on ovarian function among long‐term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy.

… The ovarian function could be determined in 111 patients. In the GnRH-a/chemotherapy … BEACOPP/GnRH-a cotreatment resumed cyclic ovarian function versus 9 of the 14 in the …

… For this reason, it comes into question whether the gonadal function and therefore the ovarian reserve is also reduced in women with HL or NHL. A reduced ovarian function is clinically …

… ovarian function recovers immediately after treatment or who maintain ovarian function, may … a late medical consequence in women treated for Hodgkin's lymphoma and, furthermore, to …

PURPOSE The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) in early responders on the basis of a positron emission tomography (PET)–driven strategy was safe and minimized toxicity compared with standard 6 BEACOPPescalated cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old. METHODS Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up. RESULTS A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; P = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, P = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPPescalated group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; P < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; P = .004). CONCLUSION Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.

To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [ 95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

… The aim of this study was to evaluate the pregnancy outcomes in women with Hodgkin lymphoma (HL) diagnosis, treated between 1972 and 1999 at Department of Radiotherapy and …

The initial peak incidence of Hodgkin lymphoma (HL) occurs during reproductive years.

BACKGROUND Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic.

… and fetal outcomes of Hodgkin’s lymphoma (HL) in pregnancy. … the adjusted effect of HL on maternal and neonatal outcomes. … Figure 1 Prevalence of Hodgkin's lymphoma in pregnancy …

Abstract 94 Background: Lymphoma diagnosed during pregnancy is a rare occurrence. Further, there is heterogeneity in clinical presentation and a range of lymphoma histologies resulting in a continued deficiency of lymphoma-specific data in the literature regarding prognosis, optimal therapy, maternal complications, and fetal outcome. Methods: A comprehensive retrospective analysis was completed for patients (pts) diagnosed (dx) with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy at 9 large U.S. academic centers over a 13-year period (1998–2011). The vast majority of cases were co-managed with high-risk maternal fetal medicine. Data on maternal disease characteristics, treatment details, obstetric complications, and fetal outcomes were analyzed. Results: 88 cases were identified with complete data available in 82. The median age of pts was 31 yrs (18–40). Lymphoma dx occurred at a median of 24 weeks (wks) gestation (5–40). 15% of pts were dx during the 1st trimester, 46% during the 2nd trimester, 35% during the 3rd trimester, while 4% (n=3) of pts had a pre-existing NHL dx (follicular lymphoma (FL)). 52% (n=43) of pts had NHL and 48% (n=39) HL. Of NHL cases, 83% (n=33) were B-cell and 17% (n=10) T-cell. B-cell histologies were DLBCL n=23 (including 2 primary CNS and 1 'double hit' NHL), FL n=5 (including 1 leukemic phase FL), Burkitt's lymphoma n=3, and mixed histology n=1; T-cell histologies were anaplastic large cell n=6, PTCL not otherwise specified n=2, and T-cell/NK NHL n=2. Pts with B-cell NHL and HL were dx at a median age of 29 yrs (range, 18–40), while T-cell NHL pts were dx at a median of 34 years (19–37). MRI without gadolinium was the most common imaging modality utilized for staging. 63% of NHL and 19% of HL pts had stage III/IV disease (25% of HL with stage IIB). Pregnancy was terminated in 6 pts (n=4 aggressive NHL and n=2 HD) to enable immediate chemotherapy (five in the 1st trimester [at 5, 8, 10, 10, and 12 wks] and 1 pt in the early 2nd trimester who required high-dose methotrexate). 48 pts (63%) initiated anti-lymphoma therapy at a median of 25 wks gestation (range, 13–37) with 79% of pts initiating therapy in the 2nd trimester (see Table 1). The median gestation at time of lymphoma dx for pts who received intra-partum treatment was 20 wks vs 34 wks for pts who had therapy deferred to post-delivery (p&lt;0.0001). The overall response rate among pts who received therapy was 87% (74% complete remission). Notably, gestation went to full-term in 54% with delivery occurring at a median of 37 wks (31–40). Therapy was deferred until post-delivery in 28 pts (37%) and the majority of these pregnancies were also carried to term (median delivery at 38 wks). At a median follow-up of 41 months (6–157), the 3-year PFS and OS for all pts were 79% and 89% respectively. Histology-specific 3-year PFS and OS were: B-cell NHL: 73% and 82%, respectively; T-cell NHL: 50% and 90%, respectively; and HL: 90% and 95%, respectively (Figure 1). Detailed obstetrical information was available in 59 pts. There were minimal pre-term complications, the most common being induction of labor in 45%. Perinatal events included spontaneous rupture of membranes in 5% and pre-eclampsia in 8%. Further, there were no differences in these events detected among pts who received intra-partum treatment vs deferred therapy. No episodes of chorioamnionitis or endometritis were noted. There was 1 stillbirth that occurred at 19 wks gestation in a 34-year-old pt with double-hit NHL following 1 cycle of R-CHOP. The median birth weight of infants was 2427 grams (1005–5262) with no difference among pts who received intra-partum chemotherapy vs not (2637 grams vs 2212 grams, respectively; p=NS). Microcephaly was reported in 1 case following 4 intra-partum cycles of CHOP for DLBCL; there were otherwise no malformations detected. Conclusions: To our knowledge, this represents one of the largest experiences reported of lymphoma in pregnancy. Our data show that standard NHL and HL chemotherapeutic regimens (without anti-metabolites) administered during the 2nd and 3rd trimester, including as early as 13 wks gestation in select cases, is associated with minimal maternal complications or fetal detriment. In addition, pts with low risk clinical scenarios (e.g., indolent NHL and/or late gestational dx) had therapy safely deferred to post-partum. In our experience, this approach was associated with overall expected lymphoma-related survival. Disclosures: No relevant conflicts of interest to declare.

Background To assess maternal and fetal outcome of women and newborns who received chemotherapy during pregnancy to treat Hodgkin lymphoma (HL)in early stages (IA, IIA), we performed a retrospective analysis of a cohort of 44 pregnant women with HL and early stages, diagnosed and treated between 1988 to 2013, at a tertiary reference cancer center. Methods We analyzed data on HL characteristics and treatment, with a particular attention to maternal and fetal complications; in children, we performed a longer follow-up to detect any anomaly in physical development, scholar performance, psychological, cardiac, neurological function, and intelligence tests. Results Median age was 29.4 (range 21–37) years; Most patients were stage IIA (86%), had M a bulky mediastinal disease (78%) and 60% had > 3 nodal sites involved; thus these patients were considered to have a not favorable condition. Abortion was refused when it was proposed. All patients received chemotherapy during pregnancy; ABVD (adryamicin, bleomycin, vinblastine, and dacarbazine) at standard doses and schedule, even during the first trimester. Radiotherapy, when indicated, was administered after delivery in 39 patients. No obstetrical complications were observed, delivery occurred between 33 to 36 weeks in 10 cases (22%); and >37 weeks in 34 cases (87%). Four newborns were low-weight: 2012 g median (range 1750 – 2350 g). No clinical malformations were observed, and development of newborns was physiological without evidence of cardiac and neurological damage, behavior, intelligence, and scholar attendance were normal. At median follow-up range of 120.4 (48–299) months, the progression-free survival and overall survival of patients were 95% and 93%respectively Conclusion Combined chemotherapy, as initial therapy appears to be the best approach in this setting of patients, with an excellent outcome to both mothers and children. If radiotherapy is necessary, it could be administered after delivery.

Hodgkin lymphoma (HL) occuring during pregnancy is a rare condition, and management relies on sparse literature. The specificity of pregnancy requires the clinician to take into account the clinical emergency, the stage of the lymphoma, the trimester of pregnancy, and the patient's choices. The main objective is twofold: to limit the risk of toxicity and adverse events for both mother and fetus, without reducing the chances of a successful outcome. Current literature data suggest that the use of ABVD-type polychemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is associated with obstetrical events and long-term fetal toxicity. We report here the results of a homogeneous management considering wait-and-see, vinblastine monotherapy and ABVD polychemotherapy options. The outcomes in terms of obstetrical complications, response rate, and overall survival (100%) reinforce the idea that strategies that do not involve the use of multidrug therapy are possible and are associated with very good results.

… Lymphoma is the fourth most frequent cancer that occurs during pregnancy, with Hodgkin lymphoma … consistent with the expected lymphoma-related outcomes. In univariate analyses of …

… patients with HL during the first trimester over the past 25 years in the British Columbia Cancer Agency with all cases reporting good pregnancy outcomes.42 In infrequent cases, when …

By means of a mail questionnaire, information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals. Seven patients conceived while receiving treatment for their neoplasms; in 22 patients, the hematologic disease was diagnosed during pregnancy, and the remaining 27 patients became pregnant after completion of the antineoplastic treatment. When a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population, no increase in the incidence of complications was observed: 64% of the pregnancies went to term, 9% resulted in spontaneous abortion, and 5% resulted in premature births. The observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals. There were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy. In spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed, the data here support the hypothesis that the cytostatic treatment of hematologic malignancies, if deemed necessary, should not be postponed because of pregnancy. Moreover, the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided, especially to those fields involving the pelvic area.

… However, in some additional cases, the maternal charts reported details of pregnancy outcome (Table I). No differences were found between the babies born to women with HD when …

Abstract As long-term survival is high for children and young adults diagnosed with leukemia and lymphoma, delineating maternal, fetal and offspring health risks is important to their family planning. This systematic review examined data comparing these health risks between leukemia and lymphoma survivors and women without a history of cancer. Following a search of Embase, PubMed, CINAHL, Cochrane, and Web of Science, 142 articles were screened and 18 were included in this review. No higher risks of spontaneous abortion, maternal diabetes and anemia, stillbirth, birth defects, or childhood cancer in offspring were observed in survivors compared to controls. Important to counseling and clinical care, live birth rates were lower, while preterm birth and low birth weight risks were modestly higher in survivors compared to controls. Findings were largely reassuring but highlight the lack of data on maternal cardiopulmonary risks, differential risk by cancer treatment type, and interventions to decrease these risks.

PurposeFertility preservation methods are playing an increasing role in women up to the age of 40 years because of rising survival rates in those affected by cancer. However, balanced practical recommendations concerning all relevant fertility preservation, to support doctors in counselling and treating patients, are still rare.MethodsThese recommendations were prepared by the network FertiPROTEKT (http://www.fertiprotect.eu), a collaboration of around 70 centres in Germany, Switzerland and Austria. The recommendations were developed by specialists in reproductive medicine, reproductive biology and oncology, which gave a comprehensive overview of all named techniques as well as their benefits and risks. Furthermore, practice-orientated recommendations for the individual use of fertility preservation methods for various indications such as breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours are given.ResultsVarious options such as ovarian stimulation and cryopreservation of unfertilised or fertilised oocytes, cryopreservation and transplantation of ovarian tissue, GnRH-agonist administration and transposition of the ovaries can be offered. All the techniques can be performed alone or in combination within a maximum of 2 weeks with low risk and different success rates.ConclusionsFertility preservation in women has become an option with realistic chances to become pregnant after cytotoxic therapies. The information provided allows a well balanced and realistic counselling and treatment.

In total, 80%–90% of Hodgkin’s lymphoma (HL) patients are curable with combination chemoradiotherapy. Due to improvements in therapeutic strategies, 50% of all relapsed/refractory patients may undergo complete clinical responses and have long-term survival. Treatment options for HL are effective, but may have a negative impact on post-chemotherapy fertility. Thus, cryopreservation of semen prior to treatment is recommended for male patients. For female patients, assisted reproductive techniques (ART) consult and fertility preservation should be offered as a therapeutical option. In the last years, new targeted molecules have been available for HL treatment. These new drugs showed a high rate of overall responses in the setting of heavily pretreated patients, most of them in relapse after autologous stem cell transplantation, a group previously considered very poor risk. Up to 50% of patients have a complete response and an improved overall survival. Future studies will address the usefulness of novel molecules as a frontline therapy. Considering the high response and survival rates with monoclonal antibody-based therapeutics, fertility has become a concerning issue for long-term HL survivors. As progress has been made regarding ART, with the rigorous steps planned for HL patients, more survivors will become parents.

… and other specialists working with young patients at risk of premature ovarian insufficiency (POI) or testicular dysfunction (TD) due to treatment of Hodgkin or Non-Hodgkin lymphoma. …

Most cancer treatments like chemotherapy, radiotherapy or a combination of both are highly toxic to the gonads, putting girls and young women at risk of premature ovarian insufficiency and subsequent infertility. Non‐oncological conditions may also require therapies that put women's reproductive potential at risk. Fertility preservation counseling should therefore be offered to all patients requiring gonadotoxic treatments, and to those who wish to postpone motherhood for social/personal reasons. Among the most effective fertility preservation options available today, oocyte and embryo cryopreservation, and ovarian tissue cryopreservation have emerged as the front‐runners.

… Our study cohort included 105 HL patients who underwent fertility preservation before starting CT (Fig. 1). We verified that there was no association between disease stage and basal …

Abstract Aim: The aim of this article is to provide the health professionals with clear, novel and practical guidelines regarding management of fertility in patients with malignant hematological disorders, with special accent on lymphoma. Also, it aims at raising consciousness of all physicians administering chemotherapy, about the undesired effects of many chemotherapy regimens, on the reproductive ability, about available methods for preserving fertility and regarding many other issues in connection with fertility in patients treated for lymphoma. Materials and methods: Online internet databases and publications have been searched, and a systematic literature review has been performed, using the following keywords: fertility, chemotherapy as well as relevant keywords in connection to the subject. Results: Within the search, reports regarding smaller-sized groups, as well as in series of patients and case reports have been found, but relatively few large randomized studies or actual reports regarding the success rate and the influence of methods for fertility preservation in patients treated for Hodgkin's and Non-Hodgkin's lymphoma. We have managed in summarizing a large proportion of the research studies and transferring it into an integral multidisciplinary text, offering valid and applicable options for fertility preservation in patients treated for lymphoma. We use the term lymphoma in general, since the chemotherapy and radiotherapy approaches for Hodgkin's and for Non-Hodgkin's lymphomas are similar, rendering a major part of the fertility preservation guidelines appropriate for both entities. Recommendations: Hematologists should possess fundamental knowledge regarding the late complications of lymphoma treatment. Besides acknowledging the risk of secondary cancer development as well as of non-neoplastic cardiac and pulmonary complications, they should be prepared to raise the issue of infertility as an integral part of the treatment plan, since that is a complication of significant importance for patients treated with chemotherapy within their reproductive life period. Possible methods for preserving fertility should be presented and discussed, and patients should be referred promptly to a reproductive medicine specialist. Cryopreservation of both sperm and embryos are considered standard practice and are generally available, while other methods are still in investigational phase and performed in specialized centers under mandatory professional surveillance and expertise. Conclusion: It is recommended to utilize treatments that are with as little as possible gonadal toxicity, to consider a wide array of options for fertility preservation as soon as possible, and to practice a decision-making process most beneficial for the patient, based on the latest medical accomplishments and most novel prospects.

Introduction Fertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship. Methods For the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel’s activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin’s lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology. Results From the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations. Discussion These recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway.

Background: Improvement in the prognosis of lymphomas in recent decades has allowed focus on reducing long-term toxicity of treatment, including infertility. The aim of this study was to assess the fertility preservation knowledge and practices among hematologic centers affiliated with Fondazione Italiana Linfomi (FIL) in Italy. Methods: A survey questionnaire was provided to 152 FIL centers between December 2019 and December 2020. Results: Responses from 58 centers (38%) were received. All respondents reported informing patients about treatment-related gonadotoxicity. A minority of patients (10% female, 20% male) refused fertility preservation due to personal reasons. The most common fertility preservation options offered to female patients were mature oocyte cryopreservation (43.1%), ovarian tissue cryopreservation (6.9%), and mature oocyte or ovarian tissue cryopreservation (39.7%). Six centers (10.3%) did not perform any procedures. All centers offered sperm cryopreservation for male patients. Challenges regarding the time intervals between lymphoma diagnosis and fertility consultation (up to 20 days) as well as between consultation and fertility preservation procedure (up to 40 days) were revealed. Conclusions: This survey provides insight into fertility preservation practices among Italian hematologic centers and points out an urgent need to improve close cooperation between hematologists and fertility preservation specialists in order to avoid unacceptable delays in lymphoma treatment.

STUDY QUESTION How do hematological characteristics affect ovarian reserve, ovarian response to ovarian stimulation, and fertility outcomes? SUMMARY ANSWER Although lymphoma characteristics impact serum AMH levels, they do not affect, per se, the response to ovarian stimulation and the number of mature oocytes recovered at the time of fertility preservation; in addition, fertility in survivors of hematologic malignancies is relatively conserved. WHAT IS KNOWN ALREADY Hematologic cancers can affect young women of reproductive age. While survival rates have improved over the years due to advances in treatment protocols, the treatments used can impact fertility. Fertility preservation methods, such as oocyte or ovarian tissue cryopreservation, are increasingly offered, but concerns remain about reduced ovarian reserve and response to ovarian stimulation in women with these cancers, which may influence the effectiveness of fertility preservation strategies. Moreover, fertility potential after hematologic cancers has been poorly studied. STUDY DESIGN, SIZE, DURATION This is a retrospective, observational bi-centric cohort study. All patients with hematologic cancer (lymphoma, leukemia, myeloma, and myelodysplastic syndrome) who underwent fertility preservation before gonadotoxic treatment (n = 286) from January 2013 to March 2023 were included. For fertility after cancer, and use of frozen oocytes/embryos, the endpoint date was 7 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS Only patients with lymphoma were included for analysis of ovarian reserve (n = 238) and ovarian response to ovarian stimulation (n = 230). Low ovarian reserve and impaired ovarian response to ovarian stimulation were defined as AMH &amp;lt;1.2 ng/ml and ≤9 mature oocytes retrieved after ovarian stimulation, respectively, according to POSEIDON criteria. A Cox regression model was used to determine predictive factors of impaired response to ovarian stimulation, low ovarian reserve, and pregnancy after cancer. Cumulative incidence of pregnancy and cumulative use of frozen oocytes/embryos was calculated in all patients suffering from hematological malignancies. MAIN RESULTS AND THE ROLE OF CHANCE There was an impact of lymphoma characteristics on AMH levels independent of age. After adjustment based on POSEIDON Groups 3 and 4, no specific impact of lymphoma characteristics (e.g. stage, clinical, or biologic B signs) on ovarian response to ovarian stimulation was observed. Regarding post-cancer fertility in the whole population, among the women who tried to conceive, 62% achieved at least one pregnancy, and 85% of these occurred naturally. After adjustment, positive predictive factors for pregnancy were age &amp;lt;35 years, being in a relationship at the first oncofertility consultation, and absence of hematopoietic stem cell transplantation. LIMITATIONS, REASONS FOR CAUTION Limitations include potential biases due to the heterogeneity of hematological conditions and the retrospective design, which may lead to missing data. Additionally, the duration of follow-up may not be sufficient to evaluate long-term fertility outcomes. WIDER IMPLICATIONS OF THE FINDINGS Lymphoma characteristics did not affect the response to ovarian stimulation in terms of mature oocyte retrieval, although AMH levels were impaired. Reassuring post-cancer fertility data support informed decision-making regarding fertility preservation techniques. Larger prospective studies are needed to tailor oncofertility counseling, ensuring optimized care and reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S) Medical editorial support was provided by Peter Todd of Tajut Ltd (Kaiapoi, New Zealand) and was funded by AFPR (Advances in Fertility Preservation and Reproduction). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

… FP was offered most to males with Hodgkin lymphoma (30.4… sarcoma (21.7%), and non-Hodgkin lymphoma (20.0%). For the … by Hodgkin lymphoma (7.8%), with nonHodgkin lymphoma, …

Female fertility preservation provides significantly different challenges to that for the male, with the only established method being cryopreservation of embryos thus necessitating the involvement of a male. Other, experimental, options include oocyte or ovarian tissue cryopreservation. The latter has been regarded as a potential method for more than a decade, but has resulted in the birth of only five babies. It is not possible to be certain how many women have had ovarian tissue cryopreserved. Oocyte cryopreservation also remains experimental, but ∼100-fold more babies have been born through this technique over the last two decades. Ovarian tissue cryopreservation has the potential advantages of preservation of a large number of oocytes within primordial follicles, it does not require hormonal stimulation when time is short and indeed may be appropriate for the pre-pubertal. Disadvantages include the need for an invasive procedure, and the uncertain risk of ovarian contamination in haematological and other malignancies. We here review this approach in the context of our own experience of 36 women, highlighting issues of patient selection especially in the young, and uncertainties over the effects of cancer treatments on subsequent fertility. Of these 36 women, 11 have died but 5 have had spontaneous pregnancies. So far, none have requested reimplantation of their stored ovarian tissue. Ovarian cryopreservation appears to be a potentially valuable method for fertility preservation, but the indications and approaches best used remain unclear.

Simple Summary Most children diagnosed with (classical) Hodgkin lymphoma survive, but chemotherapy and radiotherapy can harm their fertility. There are several fertility-preserving treatments available that can be used in effort to preserve reproductive ability. In this observational study, we studied how often fertility-preserving treatments were used in a cohort of children with newly diagnosed classical Hodgkin lymphoma and evaluated the patient- and treatment characteristics of those receiving such co-treatments. Furthermore, we surveyed patients and parents/guardians to gain insight into their opinion and satisfaction on the offered fertility counseling. Most patients and parents/guardians had received fertility counseling. Most participants were satisfied about the offered counseling and found it important. Concerns about (future) fertility were common. This study emphasizes the importance of fertility counseling and the consideration of fertility preservation based on the expected risk of infertility and patient characteristics. The evaluation of fertility care is important considering the impact of (in)fertility on quality of life. Abstract Purpose: The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL). Methods: In this observational study, boys and girls with cHL aged ≤ 18 years with scheduled treatment according to the EuroNet-PHL-C2 protocol were recruited from 18 sites (5 countries), between January 2017 and September 2021. In 2023, a subset of Dutch participants (aged ≥ 12 years at time of diagnosis) and parents/guardians were surveyed regarding fertility counseling. Results: A total of 101 boys and 104 girls were included. Most post-pubertal boys opted for semen cryopreservation pre-treatment (85% of expected). Invasive FP treatments were occasionally chosen for patients at a relatively low risk of fertility based on scheduled alkylating agent exposure (4/5 testicular biopsy, 4/4 oocyte, and 11/11 ovarian tissue cryopreservation). A total of 17 post-menarchal girls (20%) received GnRH-analogue co-treatment. Furthermore, 33/84 parents and 26/63 patients responded to the questionnaire. Most reported receiving fertility counseling (97%/89%). Statements regarding the timing and content of counseling were generally positive. Parents and patients considered fertility counseling important (94%/87% (strongly agreed) and most expressed concerns about (their child’s) fertility (at diagnosis 69%/46%, at present: 59%/42%). Conclusion: Systematic fertility counseling is crucial for all pediatric cHL patients and their families. FP treatment should be considered depending on the anticipated risk and patient factors. We encourage the development of a decision aid for FP in pediatric oncology.

Abstract Patients with non-Hodgkin lymphoma (NHL), especially younger individuals, can face fertility risks from treatment. We assessed rates and predictors of fertility counseling and preservation in this population. The LEO cohort prospectively enrolled newly diagnosed NHL patients (2015–2020) at eight U.S. academic centers. We assessed responses to a 3-year survivorship questionnaire in those aged 18–50 at diagnosis; logistic regression evaluated predictors of fertility counseling. Of 77 respondents included (46% female, median age 40), 72.2% of females and 58.5% of males recalled having a fertility discussion at diagnosis. Fertility counseling was more likely to occur in those aged 18–39 versus 40–50 (OR 10.2, 95% CI 3.3–39.2) and in those receiving alkylating therapy (OR 9.0, 95% CI 2.3–45.5). Interventions are still needed to ensure adequate survivorship care.

… cause significant distress in younger cancer survivors [4, 5]. … after being diagnosed with Hodgkin lymphoma. We include … young adolescent patients for oncofertility, we should counsel …

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.

Fertility preservation has become a critical element in the management of patients with hematologic malignancies. Although fertility in lymphoma survivors has been investigated in numerous studies, the overall quality of evidence remains low. The present investigation was designed to assess ovarian response in patients with lymphoma before oncologic therapy, comparing them with healthy controls and evaluating differences between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) subgroups. This is a retrospective, age-matched controlled study. All patients diagnosed with HL or NHL who underwent oocyte or embryo cryopreservation between October 2015 and March 2024 were included. The control cohort comprised healthy women who underwent ovarian stimulation during the same period. The primary outcome was total oocytes retrieved. Based on anti-Müllerian hormone values, the study’s statistical power is 80%. A total of 65 patients with lymphoma were enrolled. The control cohort Likewise comprised 65 age-matched individuals. The primary outcome was total oocytes retrieved. The secondary outcome was total number of mature oocytes. The gonadotropin dose and duration of ovarian stimulation were significantly greater in the lymphoma group (P = 0.001). No significant differences were observed in the total oocytes retrieved. The number of metaphase two oocytes and the proportion of mature oocytes to total retrieved oocytes were significantly higher in the lymphoma group (P = 0.013 and P = 0.026, respectively). No significant intergroup differences were observed in the numbers of 2PN, embryos obtained, fertilization rates, or embryo quality. HL and NHL patients exhibit a favorable ovarian response to stimulation prior to gonadotoxic therapy. It is therefore recommended that comprehensive counseling be provided to ensure these patients can maximize their use of fertility preservation services prior to gonadotoxic treatment.

… Female; 17 years old; Hodgkin lymphoma “Sometimes I think about … could it be passed down to my child if I had a child? She [oncologist] says no because it's not a hereditary thing, …

Improved survival of pediatric and adolescent patients with hematologic malignancies has shifted attention toward long-term quality-of-life outcomes, including fertility. Female survivors of leukemia and lymphoma are at high risk of gonadal and uterine damage due to exposure to alkylating agents, radiotherapy, and hematopoietic stem cell transplantation, resulting in premature ovarian insufficiency, diminished ovarian reserve, and adverse pregnancy outcomes. Concurrently, fertility preservation strategies have evolved, expanding options for both prepubertal and postpubertal patients. This narrative review summarizes the impact of contemporary hematologic treatments on female reproductive function and critically appraises current fertility preservation approaches, including oocyte cryopreservation, ovarian tissue cryopreservation, ovarian transposition, and pharmacologic ovarian suppression. We also review evidence on spontaneous fertility and pregnancy outcomes in survivors and discuss the specific challenges associated with hematologic malignancies, such as treatment urgency and the risk of malignant cell reintroduction following ovarian tissue transplantation. Finally, emerging strategies, including artificial ovary construction and in vitro follicle growth, are briefly addressed. Integrating early, multidisciplinary oncofertility counseling into standard care is essential to optimize reproductive outcomes and ensure equitable access to fertility preservation for young cancer survivors.

… toxicity following therapy for Hodgkin's disease, only a few data are known about gonadal toxicity of patients with non-Hodgkin's lymphoma. … , no effects on gonadal function were found …

Gonadal function in patients treated for Hodgkin's disease in childhood Background. The long-term survival of patients treated for Hodgkin's disease (HD) in childhood is high and the chief concern is now being directed toward the late effects of the treatment, including the endocrine dysfunction. Patients and methods. Testicular and ovarian functions were assessed in 64 long term survivors (24 females, 40 males) treated for HD in childhood in Slovenia between 1972 and 1994. At diagnosis they were 3-16 years old and had gonadal evaluation 4-27 years later at the age of 13-34. Fifty-four (84%) patients received chemotherapy (ChT), 49 in combination with radiation therapy (RT), 10 received RT alone. Gonadal function was assessed by the clinical examination and measurement of serum concentrations of estradiol and testosterone. Serum levels of LH and FSH were determined in the basal state and after the stimulation. Results. Primary hypogonadism (PH) was found in 30 (47%) patients. Twenty-four of 40 (60%) males had PH with evidence of damage of germinal epithelium, 4 of them had evidence of damage of Leydig cells (LC) and 10 had evidence of dysfunction of LC as well. PH was found in 6 of 24 (25%) females. Conclusions. After therapy for HD PH was more frequent in males than in females. Not only RT but also alkylating agents and procarbazine alone caused damage of LC. Age of patient at the time of treatment was not an important risk factor for gonadal toxicity. Pelvic RT in combination with ChT is the most important risk factor of the development PH both, in males and females.

… Hodgkin's disease and five from non-Hodgkin's lymphoma. … of Hodgkin’s disease and non-Hodgkin’s lymphoma with … for lymphoma has focused attention on the gonadal toxicity of the …

… toxicity after childhood Hodgkin's lymphoma depends on the type of treatment. Gonadal … , concerning male gonadal dysfunction after childhood Hodgkin's lymphoma treatment in …

Gonadal function was assessed in 101 postpubertal subjects after chemotherapy for childhood Hodgkin's disease. All had received ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone) chemotherapy alone, with no radiotherapy below the diaphragm. Gonadotropin levels were available in 46 (79.3%) male and 32 (74.4%) female subjects. The mean age at diagnosis in the male cohort was 12.2 years (range 8.2-15.3) and in the females 13.0 years (9.0-15.2). The males and the females were studied at a median of 6 years (range 2.5-11.1) and 4.3 years (range 1.9-11.5) from diagnosis, respectively. Forty-one (89.1%) male subjects had elevated follicle-stimulating hormone (FSH) levels, confirming severe germinal epithelial damage. Germinal epithelial damage was seen in subjects up to 10 years out of therapy. Subtle Leydig cell dysfunction was identified in 24.4% with raised luteinzing hormone (LH) levels. All subjects, however, progressed spontaneously through puberty. Seventeen (53%) women had raised gonadotropin levels, with variable estradiol levels. Of these, 10 subjects presented with symptomatic ovarian failure and 6 received hormone replacement therapy (HRT). Nine women had 11 successful pregnancies, two of whom had previously had symptoms of ovarian failure with one requiring HRT. A much higher prevalence of ovarian failure has been observed, than has previously been considered in the prepubertal and pubertal female following combination chemotherapy. These conclusions have important implications for future counseling, management, and research in this population.

… treated for renal disease or Hodgkin's disease. Chemotherapy… induced damage is proportionalto gonadal activity. Further … use of agents that have toxic effects on the gonad. In these …

… with acute lymphoblastic leukemia, Hodgkin's disease, gestational … gonadal toxicity and discuss how particular drug classes, doses, or combinations correlate with the degree of gonadal …

BACKGROUND: Gonadal function in pediatric and young adult survivors of Hodgkin disease is not very well defined. This study evaluates the outcome following the Multiple Drug Protocol (MDP) and the results are compared to the published experience. PROCEDURE: Ovarian and testicular function was assessed in 65 patients (36 males) with Hodgkin disease in first or second complete remission after treatment with either radiation (RT, n = 13), chemotherapy (CT, n = 9), or both (n = 43). Chemotherapy consisted of six cycles of the MDP (doxorubicin, procarbazine, prednisone, vincristine, and cyclophosphamide). Median age at diagnosis was 13.1 years (range, 2.4-22.6) and median age at evaluation was 22.6 years (range, 15.1-33.7), which was 6.7 years (range, 2.0-19.8) after the completion of all treatments. For the purpose of analysis, patients were divided into three groups: group A, patients who received only RT that did not include the pelvis (8 females, 5 males); group B, patients who received CT but no pelvic RT (15 females, 25 males); and group C, patients who received CT plus pelvic RT (6 females, 6 males). RESULTS: All patients progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25, and 5/6 and testicular volume was decreased in 1/3, 4/11, and 2/3 group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 91% and 88% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone, respectively. FSH and LH were increased in 0/8, 3/15, and 2/6 group A, B, and C female patients, respectively, at last follow-up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. Six females delivered eight normal children. CONCLUSIONS: The majority of males who received CT +/- RT have evidence of germ cell dysfunction, while Leydig cell function is unaffected in most. In females, although abnormal function early after the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential.

… AMH levels and FSH levels in Hodgkin lymphoma patients treated with or without MOPP vs. normal controls in relation to age. Solid lines, Mean healthy controls; dashed lines, 95% …

ABSTRACT Fertility is a concern in young female survivors of hematological malignancies. We evaluated post-treatment ovarian function in patients by measuring anti-Müllerian hormone (AMH) and conventional hormone levels to correlate with menstruation and fertility. The prospective cohort study included 29 reproductive-aged women diagnosed with Hodgkin lymphoma (n = 11), non-Hodgkin lymphoma (n = 9) or acute myeloid leukemia (n = 9). Hormone assays were measured after treatment was completed and compared to age-matched healthy controls. Menstrual changes and postmenopausal symptoms were assessed annually. Serum AMH levels were significantly lower compared to controls at 12 months after treatment [1.0 (0.18–1.8) vs. 2.2 (1.8–4.8) ng/mL; P < .001). At 12 months, FSH and LH levels were significantly higher compared to controls. The interruption of menstrual cycles was observed in 80% (22/27) of patients. Normal menstruation returned at a median of 1.5 months after cessation of treatment in 71% of patients, while 29% of patients had persistent amenorrhea. Low AMH levels at 12 months after therapy (<1 ng/mL) correlated more strongly with abnormal menstrual cycles than normal AMH levels (46% vs. 0%, P = .04). Four patients with low AMH consulted an infertility clinic. In summary, low serum AMH at 12 months after chemotherapy was associated with persistent menstrual abnormalities.

… cases of Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (… Finally, one should keep in mind that the AMH levels tend to … when analyzing AMH levels in our lymphoma group in …

Abstract STUDY QUESTION What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2–5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S) The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Acute lymphoblastic leukemia (ALL) and other hematological malignancies are the most common cancers in children, with chemotherapy and/or radiotherapy as the primary treatment options. These treatments, however, may have long-term effects on ovarian function and fertility in female survivors. This study aims to evaluate ovarian function and reserve in female survivors of childhood hematological malignancies by assessing hormonal markers and ovarian follicle count. This cross-sectional study included 30 female survivors of acute leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) who completed chemotherapy between 2013 and 2023. Hormonal markers including anti-Müllerian hormone (AMH), inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and ovarian follicle counts were measured. Statistical analysis was performed using SPSS, with a significance level of p < 0.05. Out of 263 patients diagnosed with hematological malignancies during the study period, 30 female patients were included. The median age at diagnosis was 14 years (range: 7–24 years). The malignancy breakdown was as follows: 7 patients (23.3%) with ALL, 2 patients (6.7%) with acute myeloid leukemia (AML), 9 patients (30%) with HL, and 12 patients (40%) with NHL. The median number of right ovarian follicles was 6 (range: 0–13), and the median number of left ovarian follicles was 7 (range: 2–12), with a total median follicle count of 12.5 (range: 5–25). AMH levels were normal in 26 patients (86.7%) and low in 3 patients (10%), with 3 patients (10%) diagnosed with decreased ovarian reserve (DOR), defined by AMH levels < 0.96 ng/mL. Inhibin-B levels were normal in 25 patients (83.3%), elevated in 1 patient (3.3%), and low in 4 patients (13.3%). Significant correlations were found between AMH and inhibin-B (p = 0.005, r = 0.508), FSH and inhibin-B (p = 0.041, r = 0.375), and inhibin-B and total follicle count (p = 0.014, r = 0.444). Additionally, a significant modarate correlation between AMH levels and total follicle count was observed (p = 0.033, r = 0.396). The evaluation of ovarian reserve using AMH, inhibin B, and ovarian follicle counts provides critical insights for fertility planning in survivors of childhood cancer. Early and comprehensive assessments may improve reproductive outcomes and quality of life for these patients.

Anti-Müllerian hormone (AMH) is a very sensitive indicator of the ovarian follicular content. Chemotherapeutic agents are notoriously ovariotoxic in that they damage follicles. The aim of this systematic review was to investigate the interest of serum AMH variations in determining the acute and long-term effects of chemotherapy on the ovarian reserve. According to the PRISMA guidelines, searches were conducted on PubMed for all English language articles until December 2013. Fifteen articles that focused on dynamic variations of AMH levels before and after chemotherapy were selected. Cancer patients have significantly lower AMH after chemotherapy than age-matched controls. Longitudinal studies of AMH variations before, during and after chemotherapy provide information about the degree of follicle loss for each patient according to different chemotherapy regimens. Different patterns of AMH levels during the ovarian recovery phase make it possible to discriminate between high and low gonadotoxic chemotherapy protocols. In addition, pretreatment AMH levels are shown to predict the long-term ovarian function after the end of treatment. These results may help to better understand the ovarian toxicity mechanisms of chemotherapy and to predict the degree of the ovarian follicle loss. Therefore, it can be useful for fertility preservation strategies, fertility counseling and future family planning.

… Regular menstrual cycle was defined as menstrual cycles at regular intervals (from 20 to 35 … Menstrual cycles were checked at 12 months due to early menstrual cycle recovery in our …

The probability of maintaining ovarian function, becoming pregnant, and delivering a normal child is important to young women anticipating successful therapy for Hodgkin's disease. In this study, reproductive function was retrospectively examined in 103 women 40 years old or younger who had undergone treatment for Hodgkin's disease with total-lymphoid irradiation (TLI) alone, combination chemotherapy, or combined TLI and chemotherapy. Infertility was directly related to gonadal exposure to therapy and to age at treatment. Twenty women became pregnant after receiving total-nodal irradiation or combination chemotherapy or both. No fetal wastage occurred, and no birth defects were seen in the 24 infants born to these women. Even after intensive treatment programs, women successfully treated for Hodgkin's disease have become pregnant and delivered phenotypically normal children.

… survivors of successfully treated Hodgkin’s lymphoma (HL) are … The subject of this analysis is to evaluate the menstrual … lower likelihood of ovarian recovery than women with younger …

we aimed to determine factors which could possibly predict future ability to conceive in patients that are to be treated for Hodgkin's lymphoma. we identified the key characteristics for high probability to achieve a spontaneous pregnancy: younger age, high ovarian reserve and GnrH-a or COC during chemotherapy. Hodgkin's lymphoma is considered one of the most aggressive yet successfully treatable oncological diseases. Prevalence among younger patients and highly gonadotoxic chemotherapy regimens bring up a question of fertility preservation. The issue of predicting the future fertility potential of patients who will have undergone chemotherapy treatment is unresolved to this day. Determining the influence of different factors would allow the creation of personalized fertility preservation treatment plans for each patient. This observational study was conducted at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. It included 149 patients of reproductive age diagnosed with Hodgkin's lymphoma who had indications to chemotherapy. All of the patients signed an informed consent form prior to participation. The study included 149 participants with a mean age of 23 ± 6.08 years. All of the participants underwent chemotherapy either without (68.09%) or with ovarian protection (OP) (31.91%). The prevalent chemotherapeutic agents were Adriamycin, Oncovin and Bleomycin. The median number of cycles was 6 ± 2.62. Out of all patients 18 had a recurrence and only one died. One patient had three recurrences but after treatment she resumed her menstrual function, achieved one spontaneous pregnancy and live birth. This patient was only 21 years old with very high antral follicular count and had a very short period between recurrences, that way her treatment was performed with continuous GnRH-a protection. Out of patients without OP, 44.8% lost their menstrual function and later had to undergo assisted reproduction treatment, including oocyte donation. Menstrual function recovery rate was higher in both groups with GnRH-a and COC - 80% and 84%, respectively – but not high enough to be statistically significant. Time to recovery was 2 ± 2.57 months, with no significant difference between groups with COC, GnRH-a or without any protection. Patients aged 30 and older had a lower menstruation recovery rate (33.33%) compared to 71.08% and 75% for those younger than 30 and 20, respectively. Two more patients were prepubescent and therefore were not included in the statistical analysis but showed normal regular menses after menarche and achieved spontaneous pregnancies. Despite aforementioned results the quantity of factors does not let us draw compelling conclusions about their degree of influence; this way multifactorial analysis with more participants would be more preferable. A higher rate of pregnancies in OP group could also correlate with higher alertness and therefore earlier attempts to conceive. our findings demonstrate the need for and possibility of predictive model development. This would provide an opportunity not only to establish fertility preservation treatment options but also help in reproductive planning for those who have completed their main treatment, taking the risk of POI into consideration. not applicable