Defective sperm doubles the risk of preeclampsia | Lund University
Christian superstition insists that every person conceived is a creation of their omniscient, omnipotent god who knows and has always known, exactly who is going to be born and has an oven-ready plan for their entire existence. Each baby conceived was exactly as the Christian god intended, down to the last detail of the DNA Exactly which sperm fertilizes which egg when, is part of the god's omniscient, perfect plan.
Leaving aside the absurdity of throwing millions of sperms at a single egg to produce that conception, when only a predetermined one was going to be the winner in order to produce the predetermined genome, when a single sperm would have been just as effective, we are left with the disturbing idea that any and all genetic defects were the intended outcome of that conception; the intention of a supposedly omnibenevolent god.
Now, it might, in fact it definitely is possible for a Christian to imagine some ultimate good will come from a child with a genetic defect, but what if a defect in the sperm causes harm not just to the baby, but to the mother? Are we to conclude that a mother whose life is put at risk by a defective sperm from her partner was the intended victim of an 'all-loving' god? What possible good can come from a mother's (and almost invariably her baby's) life being in danger from something beyond her control? What possible good can come from preeclampsia?
What is preeclampsia, what causes it and what are the dangers to mother and baby from it? Preeclampsia is a serious condition that can occur during pregnancy, typically after 20 weeks of gestation. It is characterized by high blood pressure (hypertension) and signs of damage to other organ systems, most often the liver and kidneys. Preeclampsia can range from mild to severe and, if left untreated, can lead to serious complications for both the mother and the baby.There are other problems caused by the products of conception that I'll address in a moment, but first this paper by a team from Lund University, Sweden, concerning preeclampsia caused by a defective sperm. The problem is more acute in IVF where there is a greater chance of a defective sperm reaching the egg, but the problem also exists to a lesser extent in nature as a newly-discovered cause of preeclampsia.
Causes:
The exact cause of preeclampsia isn't completely understood, but it's believed to stem from problems with the development of the placenta, the organ that supplies oxygen and nutrients to the fetus. Potential contributing factors include:
- Abnormal placental development: Blood vessels in the placenta may develop or function improperly.
- Immune system disorders: An abnormal immune response may affect how the placenta functions.
- Genetic factors: Family history of preeclampsia can increase the risk.
- Maternal conditions: Conditions such as obesity, diabetes, high blood pressure, kidney disease, or autoimmune disorders can increase the risk of preeclampsia.
- First pregnancies: Women having their first pregnancy are at higher risk.
Dangers to the Mother:
- Eclampsia: If preeclampsia is not controlled, it can lead to eclampsia, a life-threatening condition that involves seizures.
- HELLP syndrome: A severe form of preeclampsia that affects the liver and blood clotting, involving Hemolysis, Elevated Liver enzymes, and Low Platelet count.
- Stroke: Very high blood pressure can increase the risk of a stroke.
- Organ damage: Preeclampsia can cause damage to organs like the liver, kidneys, and eyes.
- Placental abruption: The placenta may detach from the uterus prematurely, causing heavy bleeding and depriving the baby of oxygen.
Dangers to the Baby:
- Preterm birth: If preeclampsia becomes severe, early delivery may be necessary, which can result in complications related to premature birth (underdeveloped lungs, low birth weight).
- Fetal growth restriction: Preeclampsia can reduce blood flow to the placenta, limiting the baby’s supply of nutrients and oxygen, leading to intrauterine growth restriction (IUGR).
- Low birth weight: Babies born to mothers with preeclampsia are often smaller due to poor placental function.
- Stillbirth: In severe cases, preeclampsia can lead to stillbirth if the baby does not receive enough oxygen.
Treatment and Management:
- Monitoring: Blood pressure and organ function are closely monitored. Regular prenatal visits help catch signs of preeclampsia early.
- Medications: Medications may be given to lower blood pressure or prevent seizures (e.g., magnesium sulfate).
- Delivery: The only definitive treatment is delivery of the baby, which may be necessary if the condition worsens or becomes life-threatening.
Early detection and management are critical in reducing the risks for both the mother and the baby.
The team have just published their findings in the journal Fertility & Sterility and announced it in a Lund University news release:
Defective sperm doubles the risk of preeclampsia
For the first time, researchers have linked specific frequent defects in sperm to risk of pregnancy complications and negative impacts on the health of the baby. The study from Lund University in Sweden shows that high proportion of father’s spermatozoa possessing DNA strand breaks is associated with doubled risk of preeclampsia in women who have become pregnant by IVF. It also increases the risk of the baby being born prematurely.
Infertility is a growing problem and the number of in vitro fertilisation procedures is increasing rapidly. It is already known that women who become pregnant by assisted reproduction techniques have an increased risk of preeclampsia, repeated miscarriages and the baby being born prematurely and with a lower birth weight. Yet, the reasons behind this have not been fully understood.
Before a planned in vitro fertilisation, the man’s sperm sample is analysed for concentration, motility and morphology. But there are men who, according to this analysis, have normal sperm, but still have reduced fertility.
Amelie Stenqvist, M.D., Ph.D, lead author
Department of Obstetrics and Gynaecology
Skåne University Hospital
Malmö, Sweden.
[Dr Amelie Stenqvist] received her PhD from Lund and now works as a specialist in gynaecology and obstetrics at Skåne University Hospital in Malmö.
Around 20-30 per cent of babies born through in vitro fertilisation have fathers with damaged DNA in their sperm, as shown by elevated levels of DNA fragmentation. The DNA fragmentation index (DFI) is a measure of the amount of strand breaks in the DNA and is used to provide important new information about male fertility. Sperm with DNA damage may still be fertile, but the chances of fertilisation are lower and if the percentage of DFI exceeds 30 per cent, the chances of natural conception are close to zero.
Although current in vitro techniques mean that men with a high DFI can become fathers, until now very little has been known about the impact of DNA fragmentation on pregnancy and the health of the baby. It has been difficult to research the topic because the DFI value is not included in the standard measurements currently taken by Sweden’s fertility clinics. It also requires a large study population and access to national medical registries.
Since half of the placenta’s DNA comes from the father and placental development and function play a central role in preeclampsia, we wanted to investigate whether a high percentage of DNA damage in the sperm affected the risk of preeclampsia.
Professor Aleksander Giwercman, M.D., Ph.D., co-author
Molecular Reproductive Medicine
Department of Translational Medicine
Lund University, Malmö, Sweden.
[Aleksander Giwercman] is a professor of reproductive medicine at Lund University, a consultant at Skåne University Hospital in Malmö and one of the researchers behind ReproUnion. Aleksander Giwercman also led a research study that included 1,660 children conceived through IVF and ICSI at the Reproductive Medicine Centre in Malmö over the period 2007-2018*.
The results showed that in the 841 couples who underwent IVF, a DFI of over 20 per cent doubled the risk of the woman developing preeclampsia (10.5 per cent) and also increased the risk of premature birth. In the IVF group with a DFI below 20 per cent, there was a 4.8 per cent risk of preeclampsia, which is comparable to pregnancies that occur naturally. For couples undergoing ICSI, there was no association with preeclampsia.
Today, DFI analysis is only performed at some fertility clinics in Sweden, but we think that it should be introduced as standard at all clinics. It can give couples answers as to why they are not getting pregnant and can influence the chosen method of assisted fertilisation. Not only that, our latest results show that a DFI analysis could be used to identify high-risk pregnancies.
Professor Aleksander Giwercman.
What makes this finding even more interesting is that high DNA fragmentation in sperm is linked to the overall health of the father and is potentially treatable. Most DNA damage is caused by oxidative stress, which is an imbalance between harmful molecules and the antioxidants that protect cells. Other factors that increase DNA fragmentation include the man’s age, smoking, obesity and infections.
The next step is to identify which group of men respond best to methods to prevent and treat sperm DNA damage, and to test these methods to prevent pregnancy complications.
Amelie Stenqvist.
Publication:High sperm deoxyribonucleic acid fragmentation index is associated with an increased risk of preeclampsia following assisted reproduction treatment
Abstract
Objective
To study the association between sperm deoxyribonucleic acid fragmentation index (DFI) and the odds of preeclampsia and other adverse perinatal outcomes after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment.
Design
A prospective cohort study including infertile couples undergoing conventional IVF or ICSI treatment and their children. Data regarding preeclampsia and perinatal outcomes were derived from the Swedish National Birth Register.
Setting
University-affiliated fertility clinic.
Patient(s)
A total of 1,594 infertile couples undergoing IVF or ICSI treatment and their 1,660 children conceived by assisted reproduction.
Intervention(s)
Sperm DFI measured by Sperm Chromatin Structure Assay.
Main Outcome Measure(s)
The primary outcome was preeclampsia. The secondary outcomes were preterm birth (PTB), low birth weight, low Apgar score, and small for gestational age.
Result(s)
With a DFI level of <20% as a reference, the odds ratio (OR) of preeclampsia statistically significantly increased in the group with a DFI level of ≥20% when IVF was used as the fertilization method (OR, 2.2; 95% confidence interval, 1.1–4.4). Already at the DFI levels of ≥10%, in IVF pregnancies, the OR of preeclampsia increased in a dose-response manner, from a prevalence of 3.1% in the reference group to >10% among those with a DFI level of ≥30%. The DFI was not associated with the OR of preeclampsia in the ICSI group. In the entire cohort, a DFI level of ≥20% was associated with an increased OR of PTB (OR, 1.4; 95% confidence interval, 1.0–2.0).
Conclusion(s)
High DFI level was associated with increased odds of PTB and, in IVF pregnancies, also increased odds of preeclampsia.
An increased level of sperm deoxyribonucleic acid (DNA) fragmentation is associated with male subfertility and has been found in 25% of men from couples with unexplained infertility (1). It has been shown that a high sperm DNA fragmentation index (DFI) level is associated with decreased pregnancy rates, in vivo and in vitro, impaired embryo development, and an increased risk of miscarriage (2). Because it has been demonstrated that a spermatozoon with DNA damage can fertilize an oocyte (3), there is a concern about how this affects maternal health and perinatal outcomes. A study, on the basis of 131 pregnancies, found no association between a high DFI level and gestational age and birth weight after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (4). A study recently published by Hervás et al. (5) showed that in IVF/ICSI pregnancies, a higher but nonsignificant incidence of preeclampsia was found in women from the high sperm DNA fragmentation group. Another study on 713 pregnancies did not show any difference in prematurity or birth weight between different DFI groups after ICSI treatments (6). However, no studies have investigated how DFI affects perinatal outcomes and the risk of preeclampsia in a larger cohort of couples treated with IVF or ICSI.
Assisted reproductive technology (ART) pregnancies imply an increased risk of preeclampsia as well as preterm birth (PTB) and low birth weight (LBW) (7–9). Several known risk factors for these complications, such as advanced age and primiparity, are overrepresented among women undergoing ART. However, reliable prediction models are still lacking. Women with preeclampsia are high-risk obstetric patients, with an increased risk of delivering children with PTB and LBW and being small for gestational age (SGA) (10).
Several paternal factors are also known to affect perinatal outcomes. Advanced paternal age and paternal obesity are associated with not only an increased risk of PTB and LBW (11, 12) but also having a high DFI level (2). There are also paternal characteristics that seem to contribute to the risk of preeclampsia (13). A large Swedish cohort study identified significant importance of couple effect related to genetic interaction between the mother and father as determinants of susceptibility for preeclampsia (14). A change of male partner may reduce subsequent preeclampsia risk in a female experiencing this condition in her first pregnancy (15). On the other hand, in women not experiencing preeclampsia in their first pregnancy, change of partner may imply an increased risk at their subsequent childbearing (16). This knowledge has led to a hypothesis of the “dangerous father”—however, it is not clarified how to identify those men and which biologic paternal mechanisms are involved.
In this study, we hypothesized that a high DFI level could increase the risk of preeclampsia as well as adverse other perinatal outcomes. Therefore, in a prospective single-center study including 1,594 couples and their 1,660 ART-conceived children, combining clinical data with follow-up in Swedish national registries, the association between DFI and odds of preeclampsia, PTB, LBW, low Apgar score, and being SGA was investigated.
Stenqvist, Amelie; Bungum, Mona; Pinborg, Anja Bisgaard; Bogstad, Jeanette; Englund, Anne Lis; Grøndahl, Marie Louise; Zedeler, Anne; Hansson, Stefan R.; Giwercman, Aleksander
High sperm deoxyribonucleic acid fragmentation index is associated with an increased risk of preeclampsia following assisted reproduction treatment Fertility and Sterility (2024); doi: 10.1016/j.fertnstert.2024.08.316
Copyright: © 2024 The authors.
Published by Elsevier. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
So, if we are to believe Christians, this problem arises because their god has arranged for a sperm with broken DNA fertilise the egg because that is the intended product of sexual intercourse on that occasion. Because their god is allegedly omnipotent we must conclude that preeclampsia was the intended result with all the attendant risks to mother and baby that entails.
There are other scenarios in which fertilisation of an egg can lead to other threats to the mother's life and, since they don't result in a viable foetus we have to conclude that that was intentional also.
For example, the 'hydatidiform mole' which result when either a sperm fertilizes an empty egg, i.e., an egg with no DNA, or two sperms fertilize an egg simultaneously. If the Christian belief that a god has preordained exactly which sperm unites with the egg, then the hydatidiform mole is exactly the intended outcome:
What is a hydatidiform mole and what risks are there for the mother? Hydatidiform mole (also known as a molar pregnancy) is a rare condition that arises from abnormal fertilization, and it can carry a risk of developing into cancer. Hydatidiform moles are a type of gestational trophoblastic disease (GTD), which is a group of conditions that involve abnormal growth of trophoblasts—the cells that normally develop into the placenta.The natural explanation, which doesn’t involve gods and doesn't require us to believe in a planned outcome, is that these things are essentially random and when things go wrong, like the broken DNA in the sperm causing preeclampsia or the result being a hydatidiform mole and the high risk of cancer, are the result of pure chance in which blame and guilt and notions of sin and punishment play no part, and there is no need to explain why a god presumed to be omnibenevolent often acts more like a malevolent sadist who enjoys randomly inflicting pain and suffering on its victims, so there is no need to perform the mental gymnastics required to believe two mutually contradictory things simultaneously - not that that has ever been an obstacle to religious belief.
Types of Hydatidiform Moles:
- Complete hydatidiform mole:
- Occurs when an egg with no genetic material is fertilized by one or two sperm. Since there is no maternal DNA, all the genetic material comes from the father, leading to an abnormal placenta with no fetus.
- The placenta grows into a mass of fluid-filled cysts, resembling a bunch of grapes.
- Partial hydatidiform mole:
- Occurs when an egg is fertilized by two sperm, leading to triploidy (three sets of chromosomes instead of two). There may be some fetal tissue along with the abnormal placental growth, but the fetus is not viable.
- Unlike complete moles, partial moles may contain a fetus or fetal tissue, but they are still associated with abnormal placental development.
Risk of Cancer from Hydatidiform Moles:
The major concern with a molar pregnancy is that it can develop into a cancerous condition known as gestational trophoblastic neoplasia (GTN). The most common form of GTN is choriocarcinoma, a fast-growing cancer that can spread to other parts of the body, such as the lungs, liver, or brain.
- Complete molescarry a higher risk of developing into cancer compared to partial moles.
- Invasive mole: Some hydatidiform moles can persist and invade the uterine muscle, leading to a condition called invasive mole, which can also develop into cancer if not treated.
Risk Factors for Developing Cancer:
- Age: Women under 20 or over 35 have a higher risk.
- History of molar pregnancy: Having a previous molar pregnancy increases the risk of recurrence and subsequent cancer development.
- HCG levels: Persistently high levels of the hormone hCG (human chorionic gonadotropin), which is produced in pregnancy, can be a sign of malignant transformation.
Diagnosis and Treatment:
- Diagnosis: A molar pregnancy is usually diagnosed via ultrasound and blood tests measuring hCG levels, which are abnormally high in this condition.
- Treatment:
- The main treatment is to remove the abnormal tissue through a procedure called dilation and curettage (D&C).
- After treatment, hCG levels are monitored closely to ensure that all molar tissue has been removed and that there is no ongoing abnormal growth.
- Chemotherapy: If a hydatidiform mole develops into gestational trophoblastic neoplasia, chemotherapy is highly effective in treating the condition, especially if caught early.
Prognosis:
The good news is that even if cancer does develop, gestational trophoblastic neoplasia is one of the most treatable cancers, with a very high cure rate, especially with early diagnosis and treatment. After treatment, women can often go on to have normal pregnancies in the future.
Regular follow-ups and monitoring of hCG levels are essential to detect and treat any progression to cancer early.
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