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Marleen A E van der Kaaij,
Natacha Heutte,
Paul Meijnders,
Edwige Abeilard-Lemoisson,
Michele Spina,
Lotte C Moser,
Anouk Allgeier,
Bart Meulemans,
Brice Dubois, Arnold H M Simons, [......],
Jeanette K Doorduijn,
Catherine Sebban,
Wilma G J M Smit,
Serge Bologna,
Judith M Roesink,
Francisca Ong,
Marc P E André,
John M M Raemaekers,
Michel Henry-Amar,
Hanneke C Kluin-Nelemans
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ABSTRACT: PURPOSEWe investigated the impact of Hodgkin lymphoma (HL) on parenthood, including factors influencing parenthood probability, by comparing long-term HL survivors with matched general population controls. PATIENTS AND METHODSA Life Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in successive clinical trials. Responders were matched with controls (1:3 or 4) for sex, country, education, and year of birth (10-year groups). Controls were given an artificial date of start of treatment equal to that of their matched case. The main end point was presence of biologic children after treatment, which was evaluated by using conditional logistic regression analysis. Logistic regression analysis was used to analyze factors influencing spontaneous post-treatment parenthood.ResultsIn all, 1,654 French and Dutch survivors were matched with 6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to 0.87; P < .001) for survivors compared with controls. Of 898 survivors who were childless before treatment, 46.7% achieved post-treatment parenthood compared with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors with children before treatment, 12.4% became parents after HL treatment compared with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P < .001). Treatment with alkylating agents, second-line therapy, and age older than 35 years at treatment appeared to reduce the chances of spontaneous post-treatment parenthood. CONCLUSION
Survivors of HL had slightly but significantly fewer children after treatment than matched general population controls. The difference concerned only survivors who had children before treatment and appears to have more personal than biologic reasons. The chance of successful post-treatment parenthood was 76%.
Journal of Clinical Oncology 09/2012; · 18.37 Impact Factor
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Marleen A E van der Kaaij,
Natacha Heutte,
Paul Meijnders,
Edwige Abeilard-Lemoisson,
Michele Spina,
Elizabeth C Moser,
Anouk Allgeier,
Bart Meulemans, Arnold H M Simons,
Pieternella J Lugtenburg, [......],
Houchingue Eghbali,
Jeanette K Doorduijn,
Franck Morschhauser,
Catherine Sebban,
Judith M Roesink,
Marie Bouteloup,
Achiel Van Hoof,
John M M Raemaekers,
Michel Henry-Amar,
Hanneke C Kluin-Nelemans
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ABSTRACT: In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and age at treatment.
The Life Situation Questionnaire was sent to 1,700 women treated in European Organisation for Research and Treatment of Cancer and Groupe d'Étude des Lymphomes de l'Adulte trials between 1964 and 2004. Women treated between ages 15 and 40 years and currently not using hormonal contraceptives (n = 460) were selected to assess occurrence of POF. Cumulative POF risk was estimated using the life-table method. Predictive factors were assessed by Cox regression analysis.
Median follow-up was 16 years (range, 5 to 45 years). Cumulative risk of POF after alkylating chemotherapy was 60% (95% CI, 41% to 79%) and only 3% (95% CI, 1% to 7%) after nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine; epirubicin, bleomycin, vinblastine, and prednisone). Dose relationship between alkylating chemotherapy and POF occurrence was linear. POF risk increased by 23% per year of age at treatment. In women treated without alkylating chemotherapy at age younger than 32 years and age 32 years or older, cumulative POF risks were 3% (95% CI, 1% to 16%) and 9% (95% CI, 4% to 18%), respectively. If menstruation returned after treatment, cumulative POF risk was independent of age at treatment. Among women who ultimately developed POF, 22% had one or more children after treatment, compared with 41% of women without POF.
Nonalkylating chemotherapy carries little to no excess risk of POF. Dose-response relationships for alkylating chemotherapy and age at treatment are both linear. Timely family planning is important for women at risk of POF.
Journal of Clinical Oncology 12/2011; 30(3):291-9. · 18.37 Impact Factor
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ABSTRACT: In vitro fertilisation (IVF) usually involves controlled ovarian stimulation (COS). There is now increasing emphasis on methods that make IVF safer and more patient-friendly. Modified natural cycle (MNC)-IVF is an example of this. In MNC-IVF spontaneous ovulation is prevented with a minimal amount of hormones and spontaneous monofollicular growth is supported. As a result, there is no risk of ovarian hyperstimulation syndrome, and the risk of a multiple pregnancy is low. There is a 9.1% chance of a pregnancy after one MNC-cycle and the cumulative pregnancy rate after a maximum of 6 MNC-IVF cycles is 33.4%. The cumulative results of a maximum of 6 MNC-IVF cycles are comparable to those of the first COS-IVF treatment cycle including transfer of cryopreserved embryos produced as a result of the treatment (33.4% versus 37.7%). The risk of a twin pregnancy following MNC-IVF is 0.1%, and 18.3% following COS-IVF. This means that MNC-IVF is a good alternative for COS-IVF.
Nederlands tijdschrift voor geneeskunde 01/2010; 154(45):A2519.
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ABSTRACT: Singletons born after IVF treatment are at risk for adverse pregnancy outcome, the cause of which is unknown. The aim of the present study was to investigate the influence of ovarian stimulation on perinatal outcome.
In this single-centre retrospective study, perinatal outcome of singleton pregnancies resulting from IVF treatment with (n=106) and without ovarian stimulation (n=84) were compared. For IVF without ovarian stimulation, a modified natural cycle protocol was used.
No differences were found in pregnancy duration, proportion of prematurity and proportion of low birth weight. Mean birth weight of modified natural cycle vs standard IVF singletons was 3485 (+/-527) vs 3218 (+/-670)g; P=0.003. After adjustment for prognostic factors by linear regression analysis, the difference in birth weight remaining was 134 g; P=0.045.
Birth weights of modified natural cycle IVF singletons found in this study are higher than standard IVF singletons, suggesting that ovarian stimulation may be a causative factor in the occurrence of low birth weight in standard IVF.
European journal of obstetrics, gynecology, and reproductive biology 10/2009; 148(1):56-61. · 1.97 Impact Factor
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ABSTRACT: To study the implantation potential of unselected embryos derived from modified natural cycle IVF according to their morphological characteristics.
Cohort study.
Academic department of reproductive medicine.
A series of 449 single embryo transfers derived from modified natural cycle IVF.
None.
Ongoing implantation rate according to embryo characteristics.
The best implantation was found in embryos with 4 and 8 cells on day 2 and 3 respectively, <or=10% fragmentation, and absence of multinucleated blastomeres. In contrast to findings from other studies, we found embryos with fewer than four blastomeres on day 2 to do relatively well. Furthermore, we found the implantation potential of embryos containing multinucleated blastomeres to be less severely impaired than expected.
Findings from this study suggest that in currently used embryo scoring systems, the implantation potential of embryos with low numbers of blastomeres on day 2, as well as embryos containing multinucleated blastomeres, is underestimated. However, it is unclear whether the results of our study apply to embryos derived from controlled ovarian hyperstimulation cycles.
Fertility and sterility 05/2009; 94(2):527-34. · 3.97 Impact Factor
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Marleen A E van der Kaaij,
Natacha Heutte,
Nolwenn Le Stang,
John M M Raemaekers, Arnold H M Simons,
Patrice Carde,
Evert M Noordijk,
Christophe Fermé,
José Thomas,
Houchingue Eghbali,
Hanneke C Kluin-Nelemans,
Michel Henry-Amar
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ABSTRACT: To analyze fertility in male patients treated with various combinations of radiotherapy and chemotherapy, with or without alkylating agents, or with radiotherapy alone for Hodgkin's lymphoma.
Follicle-stimulating hormone (FSH) levels were measured in patients with early-stage upper-diaphragmatic disease enrolled in four European Organisation for Research and Treatment of Cancer (EORTC) trials (H6-H9). Median follow-up after therapy was 32 months. Patients with FSH measurement at least 12 months after end of treatment (n = 355) were selected to assess post-treatment fertility. Patients with FSH measurement 0 to 9 months after therapy (n = 349) were selected to analyze fertility recovery; of these, patients with elevated FSH (> 10 U/L; n = 101) were followed until recovery. Factors predictive for therapy-related infertility were assessed by logistic regression.
The proportion of elevated FSH was 3% and 8% in patients treated with radiotherapy only or with nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], epirubicin, bleomycin, vinblastine, prednisone [EBVP]); it was 60% (P < .001) after chemotherapy containing alkylating agents (mechlorethamine, vincristine, procarbazine, prednisone [MOPP], MOPP/doxorubicin, bleomycin, vinblastine [ABV], bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone [BEACOPP]). After a median time of 19 months, recovery of fertility occurred in 82% of patients treated without alkylating chemotherapy. This proportion was 30%, statistically (P < .001) lower in those treated with alkylating chemotherapy, and median time to recovery was 27 months. The post-treatment proportion of elevated FSH increased significantly (P < .001) with the dose of alkylating chemotherapy administered, and recovery was less frequent and slower after higher doses. Age more than 50 years and stage II disease also contributed to poor outcome.
Fertility can be secured after nonalkylating chemotherapy for Hodgkin's lymphoma. In contrast, alkylating chemotherapy has a dismal effect, even after a limited number of cycles.
Journal of Clinical Oncology 08/2007; 25(19):2825-32. · 18.37 Impact Factor
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ABSTRACT: To compare the efficacy of two early cessation protocols of triptorelin treatment in controlled ovarian hyperstimulation with the conventional long protocol in in vitro fertilization/intracytoplasmic sperm injection.
A double-blind, randomized, multicenter study.
Three Dutch hospitals.
One hundred seventy-eight women randomized to one of three treatment groups at the start of stimulation.
Midluteally started triptorelin administration was continued until the first day of hMG treatment (group S), or up to and including the fourth day of hMG treatment (group M) or the day of hCG injection (group L).
Occurrence of a premature LH surge.
One premature LH surge was observed in group M but not in groups S and L. Both early cessation protocols (S and M) are at least as effective as the long protocol (L) with regard to the number of oocytes (11.1 and 10.3 vs. 9.3), number of embryos (7.3 and 6.5 vs. 5.5), and ongoing pregnancy rate (28% and 24% vs. 21%).
Early cessation of triptorelin on day 1 of hMG treatment in a midluteally started IVF protocol is as effective as the traditional long protocol in preventing a premature LH surge and results in similar fertility effects.
Fertility and sterility 05/2005; 83(4):889-96. · 3.97 Impact Factor
