Case Report | DOI: https://doi.org/BRCA-RW-24-009

Reemphasizing The Significance of Fertility Preservation in Cancer Patients Needing Chemotherapy And /Or Radiotherapy- A Case Report

Kulvinder Kochar Kaur *

Obstt & Gynae, specialist reproductive endocrinology & Infertility specialist, India.

Abstract

Having reviewed earlier on how significant it had become to counsel both male and female patients prior to initiation of chemotherapy/radiotherapy to get either cryopreservation of sperm/ oocyte before initiating chemotherapy/radiotherapy with the escalation of 5 year survival rates in cancer survivors thus more of them needing to seek for fertility.However even till now Clinical practitioners fail to do so as emphasized by the case reported here for a male patient who received treatment at the age of 25 for non Hodgkin’s lymphoma;surgery followed by chemotherapy and radiotherapy without any counselling for semen cryopreservation as a result of which their conception was impacted by type II Arnold Chiari malformations ending in MTP.Since patients semen analysis was normal and no prior counselling it was difficult to counsel the husband how this might recur unless precautionary measures but fell on deaf ears.

Introduction:

With the greater advancements in field of cancer treatment, the survival rates have escalated remarkably, thus the need arising for the fertility preservation in the survivors with regards to oocyte/embryo/ovarian tissue / Cortical tissue/ testicular tissue transplantation/ sperm cryopreservation has assumed great   importance particularly for those receiving chemotherapy that too with alkylating agents. Furthermore, the need further is enhanced  in younger adults along with adolescents diagnosed for cancer and need chemotherapy and are yet to attain puberty where it might  not be feasible to do cryopreservation of oocytes. However even in adult cases how significant it has become for any clinical practitioners tackling patients where diagnosis of cancer is made in addition to emphasize the significance  of counselling both maleand female patients prior to initiation of chemotherapy/radiotherapy to get either  cryopreservation ofsperm/oocytebefore initiating chemotherapy/radiotherapy.We have made numerous publications regarding this issue ,however still we come across akin patients who never received any counselling keeping longterm fertility in mind .The case report we present here highlights this issue .

Case Report

A couple came to our centre on 11/2/2023 with the history of married for 9 yrs along with previously having a conception where antenatally  a diagnosis of typeII Arnold Chiari  malformations , thereby MTP was performed.Wifes age now was 40 yrs  and husband37 yrs. On in depth probing we got the history of husband obtaining  treatment for certain axillary mass which was surgically  removed  in addition to got chemotherapyx 6 cycles and  radiotherapy for4 cycles although   the nature of  chemotherapy was not known he later told diagnosis was non Hodgkin’s lymphoma.This had been done 10yrs previously.Now they had come for counselling for subsequent pregnancy  in addition to  chances for a normal child later. His RSA displayed a semen count of 70m/ml,with apparently morphology was normal in 70%.. Taking  into account there being a history of  both  chemotherapy along with radiotherapy  receipt we counselled her for Intracytoplasmic sperm injection (ICSI)in addition to preimplantation  genetic testing( PGT) for  aneuploidy(PGT-A) prior to embryo  transfer(ET)once normal   PGT report attained however  the couple were not willing to attribute this problem to chemotherapy along with radiotherapy as wellas RSA was normal they wanted simpler approach.Earlier we had reported innumerable reviews on fertility preservation in both male and  female cancer therapy with chemotherapy particular alkylating agents along with considerable research getting performed even in young children in addition  to adolescents who have not attained puberty along with any treating physician needs to refer these cases for counselling for fertility preservation as per age either gametes/testicular /ovarian cortical tissue/testicular tissue transplantation[1-5].

Why Need for Fertility Preservation:

Despite the banking of sperm prior to the initiation of cancer treatment is   recommended, conditions might be there that prevent the successful cryopreservation    of sperm in personalized  patients. The restoration of spermatogenesis subsequent to   chemotherapy or radiotherapy is  acknowledged to be unanticipable  as well as studiesof spermatogenesis in long-term cancer survivors have illustrated corroboration of continuation of  azoospermia or robust oligospermia  in approximately 24% of cases .However, the ultimately resumption of sperm generation inplethora of  posttherapy cancer patients incites the   query if the posttreatment safety of sperm utilized  in natural or via assisted  reproductive technologies(ART) on contemplating conception. Choy et al.[ 6], assessed this  problem of reproductive  safety in addition to the risks of utilizing sperm from cancer patients.

In reference to these  botherations over reproductive safety are basically based  in the plausible existence of DNA injury stimulated  by the germ line chemotherapy or radiotherapy. Chemotherapeutic agents, specifically the  alkylating agents which get commonly utilized, might   stimulate genetic injury by cross-linking DNA along with introducingsingle-strand DNA breaks; the   akin mutagenic actions of radiation originating from DNA fragmentation evoked within  cells (2, 6). The estimation of genetic safety  depends largely on the spermatogenic stage at which a mutation is  attained. In view of down-regulation of DNA repair mechanistic modes which take place in late spermatogenesis,spermatogenic cells further along the differentiation pathway  canonically do not possess the  capacity of repair DNA injury, nor do  they possess the  capacity generally  ofgoing via total apoptosis [7].Thereby the ejaculated spermatozoa might foster substantial genomic injury which theoretically might get transmitted to a resultant embryo subsequent to fertilization.Fortunately, mutations that stimulate sole stages of spermatogenesis would provide a risk period for thegeneration of genetically endangered sperm that is  restricted  to approximately 3 months/ the time taken  for a  full spermatogenic cycle to finish [7]. Conversely, mutations  suffered  by the spermatogonial stem cells possess    the capacity of plausibly healed by inherent DNA repair mechanistic modes or entirely  eliminated by the cell's apoptotic machinery. Nevertheless,since these spermatogonial cells which portray the progenitors from which all future germ lines get  obtained  , any sustaenance ofmutations in these cells dodge  repair or depletion will persistently  get  transmitted, resulting in the plausiblegeneration of mutation-carrying sperm for the full  time period of a  man's lifetime[7]. 

There is a scarcityof peer-reviewed literature in reference to reproductive results in the acute, posttreatment duration of  time. These studies are   clearly restricted in view of  ethical along with the practical botherations. Existing studies implicating humansare usually largely removed from the acute, posttreatment  time frame, and they previously canonically typically conclude that the frequency ofcongenital anomalies in the children of men earlier  having exposure   to chemotherapeutic agents is not more compared to that  observed  among the general population [rev in 6]. Nevertheless, case  studies of men who have managed to conceive subsequent to  cancer therapy continue to corroborate the plausibility of an  association between cancer therapy as well as congenital anomalies  in humans, since  instances of resultant syndactyly, tetralogy   of Fallot, in addition to anencephaly have been revealed [8]. 

Further Meistrich ML.[9]  reviewed the actions of chemotherapy as well as radiotherapy on spermatogenesis in humans.

They described the i)Course of how sperm decrease takes place(Figure1)-see ref no 9 for details.

Figure:1 : Courtesy reference no-9-Sequence, kinetics, and survival after irradiation of spermatogenic cells in the human male. Drawings cells courtesy of Dr. Y Clermont. Arrows indicate time required for cells to mature from one state to another. Numbers in parentheses are based on histological counts of the surviving fraction of cells at 2 weeks after 1 Gy of irradiation, reflecting the direct killing of cells by irradiation and 2 weeks of maturation depletion (3)
Figure 3: Courtesy reference no-9-Declines in sperm counts in patients treated with two different chemotherapy regimens. (A) NOVP (9) chemotherapy consisting of Novantrone (mitoxantrone), Oncovin (vincristine), vinblastine, and prednisone for Hodgkin's disease. Small open circles are individual sperm counts. Large filled circles are averages of counts grouped into time ranges. (Reprinted with permission from Meistrich et al., Journal of Clinical Oncology 15: 3488, 1997) The subsequent recovery of sperm counts to normal levels is also shown. (B) CY(V)ADIC (8) chemotherapy consisting of cyclophosphamide, Adriamycin (doxorubicin), DIC (DTIC, dacarbazine), with or without vincristine for Ewing and soft-tissue sarcoma. Pretreatment counts are indicated by solid symbols. Dashed lines connect longitudinal counts for individual patients. (Reprinted with permission from Meistrich et al., Cancer 70: 2703, 1992
Figure 3: Courtesy reference no-9-Recovery of sperm counts in individual patients treated with (A) hemi-pelvic radiotherapy for seminoma (2223), or (B) pelvic radiotherapy for Hodgkin's disease (24). Gonadal doses are indicated next to each plot.
Figure 4:Courtesy reference no-9- (A) Examples of delayed recovery of sperm count occurring after 2 to 5 years of azoospermia in 5 patients treated with chemotherapy agents that are toxic to stem spermatogonia. (◯,●) CVPP-ABDIC consisting of cyclophosphamide, vincristine, procarbazine, prednisone, Adriamycin, bleomycin, dacarbazine, and lomustine (CCNU) (26) treatment for Hodgkin's disease patients; (▲) CHOP-Bleo which consists of cyclophosphamide, Adriamycin (hydroxydaunorubicin), Oncovin, prednisone, and bleomycin (27) treatment for a non-Hodgkin's lymphoma. (B) Kaplan-Meier actuarial estimation of sperm count recovery to 10 million/ml showing the overall rates and extents of recovery in sarcoma patients were treated with the CY(V)ADIC regimen, but receiving different total doses of cyclophosphamide (8) (Reprinted with permission from Meistrich et al., Cancer 70: 2703, 1992)

Conclusion

Thereby our patient received the usual drugs for non Hodgkin’s lymphoma probably  in addition to  radiotherapy as well as although normal RSA as explained by ChoyJT, BranniganRE their child suffered from typeII Arnold Chiari malformationswhich adds to the list of congenital anomalies  earlier documented  in the aftermath of receiving chemotherapy and radiotherapy,thereby emphasizing on cryopreservation prior to any chemotherapy and radiotherapy to avoid such effects on the gametes and documentation of these congenital anomalies is significant for convincing the patients in addition to   treating clinical practitioners.

References

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