Parenthood and possibility #5

00:00:03: Welcome to Crystal Clear.

00:00:04: In this podcast, we share knowledge and experiences around cystinosis... ...to help make living with this chronic disease a little more manageable….

00:00:13: …and a bit easier in everyday life!

00:00:15: We're glad you are here with us.

00:00:17: Cystinosis is more than a medical diagnosis — it shapes every day-life decisions

00:00:23: hopes

00:00:24: And sometimes even future plans like the desire to have children or start a family.

00:00:30: What is possible with cystinosis?

00:00:32: Medically, practically and above all emotionally.

00:00:36: In this episode we explore the medical perspective alongside personal experiences.

00:00:41: Joining me is Dr.

00:00:42: Mira Choi from The Kidney Center Lichtenberg.

00:00:45: She offers perspectives on female fertility and reproductive health And she also manages pregnancy care and follow-up for her patients.

00:00:53: Hello Doctor Choy

00:00:55: Welcome to everyone listening.

00:00:58: Thank you so much for the opportunity to speak on this podcast!

00:01:07: Pregnancy counseling and family planning look quite different with cystinosis compared to typical pregnancies.

00:01:15: These women often have multiple coexisting conditions, not just one that requires a very high level of expertise.

00:01:26: It is essential that there's close collaboration between gynecology, obstetrics specialized outpatient clinics primary care physicians and pediatricians so everything is closely monitored.

00:01:39: And the pregnancy has the best possible chance of a successful outcome.

00:01:43: What impact does cystinosis have on fertility

00:01:47: in women?

00:01:48: Cystinosis itself at least in women Does not necessarily limit fertility particularly when kidney function is well maintained.

00:01:58: Complications arise when there are additional conditions, such as high blood pressure or significantly impaired kidney function.

00:02:07: these can cause hormonal fluctuations that affect fertility but cystinosis on its own Is not the primary factor determining whether a woman can become pregnant.

00:02:18: Are There Many Women with Cystinosis Who Have Had Children of Their Own?

00:02:23: It's difficult to give exact numbers.

00:02:26: There are no precise data available.

00:02:29: What we do know is that life expectancy for patients with cystinosis has improved significantly thanks to earlier diagnosis and early treatment.

00:02:40: The earlier treatment begins, the higher the life expectancy.

00:02:44: As a result more and more women are reaching adulthood.

00:02:51: But it's also important to consider emotional and psychological resources, And have an honest conversation about life expectancy which is highly individual.

00:03:02: When Is the optimal time for pregnancy in the presence of impaired kidney function?

00:03:07: How long should someone wait after a kidney transplant before planning a pregnancy?

00:03:12: That's

00:03:12: not easy question because its never just about Kidney Function alone.

00:03:18: Many factors play role.

00:03:19: Broadly speaking, there are two forms of kidney disease to consider.

00:03:24: First, there's acute impairment—for example following a severe infection.

00:03:29: In that case it is advisable to wait until the kidney function has stabilized.

00:03:34: Then there's chronic kidney disease which had been present for months or years and does not improve on its own.

00:03:41: The more severely kidney function is impaired... ...the greater risk of complications.

00:03:46: So the timing is more favorable when kidney function is not yet severely compromised.

00:03:51: There's a clinical guideline indicating that complication rate can be significantly elevated.

00:03:57: in pregnancies with kidney disease When creatinine levels are above two point five, complications can be expected in sixty to seventy percent of cases.

00:04:07: That means there is risk for mother as well.

00:04:10: She could experience heavier bleeding or develop preeclampsia.

00:04:14: That's when high blood pressure occurs, or there is protein loss through the kidneys along with organ complications where the cause isn't clear.

00:04:22: And that can affect liver, nervous system and eyes – it varies widely!

00:04:27: After a kidney transplant which is not uncommon in our patients….

00:04:31: The recommendation to wait at least one year In early post-transplant period, kidney function still fluctuates and immunosuppressive medications are at their highest levels, so in any case wait one year after a kidney transplant.

00:04:45: If kidney function is already significantly impaired there's a real risk it will deteriorate further during pregnancy—and in some cases the patient may even need to start dialysis.

00:04:56: In patients with cystinosis specifically, Fanconi syndrome may be present.

00:05:01: This is kidney damage that leads to massive fluid loss Electrolytes, protein.

00:05:06: all of this is lost And this creates a state of instability for the mother or patient, as well as for the kidney.

00:05:12: In that situation it's important to wait until things have stabilized before considering pregnancy.

00:05:18: and then there is special

00:05:19: case.

00:05:19: some patients

00:05:20: are already on dialysis on renal replacement therapy.

00:05:24: That's major problem

00:05:25: with detoxification

00:05:26: and daily dialysis actually recommended rather than standard three sessions per week for hemodialysis.

00:05:33: This requires close hospital based care due logistical demands involved.

00:05:37: What should be considered regarding cysteamine therapy when planning a pregnancy?

00:05:41: The oral form of cysteamine therapy, the tablets or capsules is harmful to the developing child and must not be taken during pregnancy.

00:05:52: If a pregnancy occurs, oral cysteamin must be paused for entire duration.

00:05:58: The eyedrop form of cystiumine, however does not reach significant blood levels so cystiamine eye drops can be continued throughout pregnancy.

00:06:09: What does the pause in cystamine therapy mean for patients?

00:06:13: How does it affect

00:06:14: them ?

00:06:15: The pause is quite a long one ideally covering the full forty weeks of pregnancy though It may be shorter given the elevated rate of preterm birth In this population.

00:06:27: During this time, there is a real risk that cystinosis-related damage can continue to the muscles... ...to the kidneys.

00:06:36: Kidney function can decline.

00:06:38: The direct impact of the therapy pause Is difficult to isolate from other factors of pregnancy But it's significant period of time and It can lead progression of disease.

00:06:50: What should be considered regarding therapy for patients who have not yet had a transplant versus those who've already been transplanted?

00:06:59: The severity of kidney impairment determines the risk of complications.

00:07:04: From a therapeutic standpoint, good blood pressure management and very close monitoring—monthly blood tests and ultrasound are essential.

00:07:14: There is evidence that women at elevated risk preeclampsia Taking aspirin, ASA can be protective.

00:07:22: This should ideally be started before week sixteen of pregnancy.

00:07:26: Additionally certain medications blood pressure drugs or immunosuppressants Can be harmful to the developing child and may need To be adjusted already during pregnancy planning Or at the latest once pregnancy is confirmed.

00:07:40: The treating physicians are well aware Of this And can advise accordingly.

00:07:45: How do pregnancies in patients with cystinosis typically progress?

00:07:50: Are they different?

00:07:52: Cystinosis can affect multiple organ systems, so monitoring during pregnancy must go beyond kidney function alone.

00:08:01: Fyroid function, urinary protein excretion and blood pressure all need to be carefully watched.

00:08:08: That's

00:08:08: not necessarily all that different from what we see in some other patients with complex conditions With cystinosis, it's important never to lose sight of the multi-organ nature of the disease.

00:08:21: Clinical monitoring laboratory testing and imaging including kidney and cardiac ultrasound should all be part of the care plan.

00:08:30: When Should Cystium Mean Therapy Be Restarted After Delivery And At What Dose?

00:08:35: It's recommended to restart oral cysteamine therapy immediately after delivery, given the length of pause during pregnancy.

00:08:45: You can either start at a lower dose and work up or if medication was well-tolerated before, restart right away!

00:08:55: Is it

00:08:56: safe for breastfeed while taking cysteine?

00:08:59: Breastfeeding is fundamentally important for the mother-child bond and is generally encouraged.

00:09:06: Regarding the transfer of systamine into breast milk, there are some indications that lower doses may not be significantly problematic but we do not know for certain And There Is A Risk That The Medication Could Pass Into The Breast Milk & Reach The Newborn.

00:09:23: This needs to be discussed carefully on an individual basis, weighing the importance of breastfeeding against the need to restart full-dose systemine therapy.

00:09:33: I would say that given the patient already had numerous organ complications and it is very important to resume the full dose immediately after delivery... ...I would be somewhat cautious but this is something that needs to been discussed with a patient on case by cases basis.

00:09:49: Dr.

00:09:50: Choi How did you first come into contact with cystinosis?

00:09:54: Before joining the Kidney Center Lichtenberg, I worked for many years at The Charité in Berlin specifically in transplant medicine including follow-up care for patients after kidney transplantation.

00:10:08: I worked in a specialized outpatient clinic and met my first three patients with Cystinosis.

00:10:15: that was when i began to engage more deeply and reached out to Dr.

00:10:20: Hohenfeldner, to exchange knowledge.

00:10:22: then one of my patients became unexpectedly pregnant which prompted me to immerse myself even more intensively in the subject.

00:10:31: through that experience I learned a great deal.

00:10:34: we also regularly care for many kidney transplanted women during pregnancy Which has given us substantial experience In this area.

00:10:43: That is how i found My way into This very specialized field.

00:10:47: Thank you so much, Dr.

00:10:49: Mira Choi from the Kidney Center Lichtenberg.

00:10:52: I'm now very pleased to welcome Doctor Yulia Rohayam.

00:10:56: She is the Chief Physician of Endocrinology and Diabetology at The Children's Hospital Of Eastern Switzerland in Saungalen.

00:11:03: Hello doctor Rohayum!

00:11:05: Hello

00:11:06: thank You for

00:11:07: having

00:11:07: me.

00:11:08: What about men with cystinosis?

00:11:10: How does the disease affect their fertility?

00:11:13: Men with cystinosis have, until recently been considered unable to father biological children.

00:11:21: At least no such cases had been documented in the medical literature.

00:11:26: However we have now conducted a more thorough investigation of this topic and found that This is not entirely The case.

00:11:34: We are now aware Of two fathers of healthy Children.

00:11:38: whom?

00:11:38: We know that the testes in young men with cystinosis gradually degenerate.

00:11:47: They become overloaded with cysteine crystals stored in the lysosomes, which are organelles found in all cells of the body.

00:11:55: This overload causes the testees to shrink progressively over the course a lifetime eventually losing their function.

00:12:03: The testes have dual functions they produce testosterone and sperm.

00:12:08: The first function, testosterone production remains relatively intact for quite some time.

00:12:14: It is typically sufficient to allow young men with cystinosis To go through puberty normally even if puberty may be somewhat delayed.

00:12:23: the second Function sperm production Is more problematic?

00:12:27: The cysteine crystals interfere With the sertoli cells and the testosterone producing cells both of which are necessary For the development of sperm from spermatogonial stem cells the precursor cells for sperm.

00:12:40: In summary, what was once seen as a hopeless situation regarding biological fatherhood now with new findings carries real hope.

00:12:49: young men with cystinosis can become fathers but they need to act in time.

00:12:54: From What Age Should Patients With Cystinosis Be Evaluated Or As You Put It Screened?

00:13:01: We know that in late puberty endocrine testicular function, meaning testosterone production is generally still preserved and a key prerequisite for sperm production Is that a man has not yet become dependent on testosterone replacement therapy?

00:13:18: Because once that threshold is crossed sperm production is no longer possible so evaluation should happen before the testes have degenerated to a point where testosterone replacement becomes necessary.

00:13:32: The earlier the search for sperm begins, the better.

00:13:36: This is typically possible once young man has reached late puberty around age sixteen when he had gone through puberty and achieved a late pubertal developmental stage.

00:13:47: That said, Evaluation can also be done at later points.

00:13:52: We have seen men in their early thirties, even men who've already had a kidney transplant.

00:13:57: Who still has a chance of sperm retrieval though not necessarily through natural means.

00:14:03: The message is this Once the young man with cystinosis reached adulthood he should ideally see an endocrinologist who will assess testosterone producing testicular function and refer him to center where semen sample can be analyzed for sperm.

00:14:20: In the early stages, sperm may still be present in the ejaculate.

00:14:24: Later in life as cysteine overload increases, sperm will likely no longer be found in the ejaculate—a condition called azospermia.

00:14:33: But even then hope is not lost!

00:14:35: In that situation it maybe possible to surgically extract sperm directly from the testes a procedure that requires general anesthesia.

00:14:44: We have found

00:14:45: that even men with no sperm and their ejaculate due to testicular degeneration from cystinosis, may still have sperm in the deeper tissue of the testes.

00:14:55: These sperm can be cryopreserved frozen and used later for assisted reproduction.

00:15:00: these surgically extracted sperm are called tz-sperm from testicular sperm extraction.

00:15:07: using this sperm biological fatherhood through assisted reproduction becomes possible.

00:15:13: The recommendation is Young men with cystinosis who can imagine wanting to become biological fathers should be evaluated at the end of puberty and no later than their early thirties.

00:15:24: And what does such an evaluation look like?

00:15:28: The first step is a hormone panel, primarily LH FSH Testosterone and inhibin B. then a semen sample is obtained.

00:15:39: That means that as a young man, you would have to go into the booth and on command produce a semen sample which will then be examined.

00:15:47: In best case sperm are present in this sample.

00:15:51: This is the case about twenty percent of late pubertal men with cystinosis.

00:15:56: In eighty percent no sperm found in ejaculate.

00:16:00: even if there isn't an ejaculation there's not any sperm in it.

00:16:05: There still is good chance earlier than better of surgically extracting sperm and freezing them for future use in assisted reproduction.

00:16:14: When the young man later finds the right partner, and decides to have a child those frozen sperm can be used.

00:16:21: What options are available for patients who want to have biological children?

00:16:26: In the favorable scenario when sperm is present in the ejaculate which occurs about twenty percent cases natural conception as possible.

00:16:35: However, this

00:16:36: is less likely in men

00:16:38: with the classic mutation found in fifty percent of Central Europeans—the fifty-seven kilobase deletion.

00:16:45: In rare cases, milder mutations may still allow sperm to be present in the ejaculate making spontaneous conception through normal intercourse possible.

00:16:54: In all other cases —the eighty percent—assisted reproduction is required.

00:16:58: This could involve freezing sperm early when quality is still sufficient or using intraceidoplasmic sperm injection ICSI, if quality is poor.

00:17:08: Sperm that has been surgically extracted and frozen can also be used for assisted reproduction.

00:17:13: In the worst case scenario where a man is older And the testes have degenerated to the point Where they could no longer produce testosterone at all Biological fatherhood Is no longer possible through his own sperm.

00:17:24: in That case donor sperm would Be only remaining option.

00:17:28: What's your advice regarding Systemine therapy from Mennon?

00:17:32: Unlike the situation in women where there is concern that systamine may be harmful to developing fetus during pregnancy, In men.

00:17:41: There's no need to discontinue systamine therapy.

00:17:46: What medications should men be aware of?

00:17:49: After a kidney transplant Men take immunosuppressive medications To prevent organ rejection.

00:17:56: These medications are not always ideal for sperm production and it is also unclear whether they might affect the genetic integrity of sperm.

00:18:06: That said, immunosuppressive therapy cannot be discontinued when trying to father a child because doing so would put the transplanted kidney at risk.

00:18:17: In short

00:18:18: for men

00:18:19: no changes to therapy are actually required.

00:18:22: You work in children's hospital.

00:18:25: Are there already children born into patients with cystinosis?

00:18:29: Yes I currently work at a children's hospital, but three years ago i worked in the Center for Reproductive Medicine at the University of Munster where we also treated adults.

00:18:42: There We actually helped two young men achieve biological fatherhood.

00:18:47: both had mild mutations and still had sperm in their ejaculate.

00:18:52: one became a father naturally.

00:18:54: The other had very few sperm in his sample and became a father through intracytoplasmic sperm injection, ISI.

00:19:01: A third man who already had a kidney transplant underwent a successful micro-TC meaning sperm were successfully found and extracted surgically from his testes.

00:19:12: In His case however the pregnancy did not come to term.

00:19:16: How Did You Come To Focus On Cystinixis?

00:19:19: Cystinosis is primarily a topic within pediatric nephrology.

00:19:24: I am a pediatric endocrinologist, Dr.

00:19:27: Hoenn Felner who previously worked at the University of Munich and now works in Rosenheim has been caring for people with cystinosis across Germany and built up a multi-disciplinary clinic.

00:19:39: She felt that the topic of fertility needed to be addressed And she reached out to me when i was working as an endocrineologist At The University Of Munster We launched a joint study, which generated the findings I have just described so that picture is no longer as bleak.

00:19:54: As it once was.

00:19:55: we now know It's possible to become a biological father with cystinosis.

00:20:00: You Just Have To Act In Time.

00:20:02: Thank you so much Dr.

00:20:04: Julia Rohayam Chief Physician of Endocrinology and Diabetology at The Children's Hospital Of Eastern Switzerland in St.

00:20:11: Gallen.

00:20:12: Let's wrap up With A Summary Of Everything We Covered Today.

00:20:16: In patients with cystinosis, kidney function has a significant influence on the course of pregnancy.

00:20:22: When planning a pregnancy it is important to seek counseling from a nephrology center in advance.

00:20:28: Systemic cysteamine therapy —the oral form— must be paused during pregnancy while cysteamine eye drops can be continued.

00:20:35: Oral cysteamin therapy should be restarted immediately after delivery.

00:20:40: regarding breastfeeding while taking cysteiamine There are no dedicated studies, but it is assumed that the amount of cystiumene in breast milk is small.

00:20:48: The option of breastfeeding should therefore be discussed individually with each patient.

00:20:53: Male patients with cystinosis frequently develop azospermia meaning no sperm are detectable in the ejaculate and their reproductive capacity is significantly limited as a result.

00:21:03: Nevertheless, It's generally possible for affected patients to have biological children.

00:21:11: We therefore recommend that all male patients present at an andrology clinic from the age of fourteen provided they are able to produce a semen sample.

00:21:19: If sperm were found in the ejaculate, the sample can be cryopreserved frozen for use at a later point if no sperm are present.

00:21:26: it should be assessed at a latter stage whether surgical sperm retrieval-for example through testicular sperm extraction or TC is option.

00:21:34: Additionally, male patients with cystinosis face an elevated risk of developing testosterone deficiency later in adult life.

00:21:41: Importantly before initiating testosterone replacement therapy it must be established whether the patient wishes to have children because testosterone therapy can further suppress whatever sperm production remains.

00:21:52: Thank you so much for listening.

00:21:54: If you'd like to learn more, the Cystenosis Foundation offers further podcast episodes and videos that provide helpful information and support for everyday life with cystenosis.

00:22:05: Do take a look!

00:22:06: And see in next episode.