Every confirmed case of nonuplets, including the most widely known birth in 2021, has involved fertility treatment rather than spontaneous conception. Specifically, the mechanism behind these pregnancies is ovarian stimulation, a class of medication that prompts the ovaries to mature and release far more eggs than the single egg typical of a natural cycle. When many of those eggs are fertilized at once, the result can be a pregnancy of extreme order. The story of how nonuplets happen is really the story of what ovarian stimulation does, why it sometimes goes further than anyone intended, and why modern reproductive medicine has been working hard to prevent it.
Ovarian Stimulation and the Release of Multiple Eggs
In a natural menstrual cycle, a single dominant follicle typically matures and releases one egg. Fertility drugs, particularly gonadotropins and clomiphene citrate, override that process by stimulating the ovaries to develop multiple follicles simultaneously. The goal is usually modest: produce a few extra eggs to improve the odds of conception for someone struggling with infertility. But the ovaries do not always respond in a predictable, controlled way. Some women are high responders, meaning their ovaries recruit a large number of follicles even at standard drug doses. If ovulation then occurs, whether naturally or triggered by an injection, all of those mature eggs can be released at once.
When ovarian stimulation is paired with timed intercourse or intrauterine insemination rather than IVF, there is no laboratory step where a clinician can limit how many embryos develop. Every released egg that meets a sperm cell in the fallopian tube has a chance of being fertilized. In a cycle where nine or more eggs mature and release, the conditions for a nonuplet pregnancy exist. This is a fundamentally different situation from IVF, where eggs are retrieved, fertilized in a dish, and a set number of embryos are transferred back into the uterus.
The 2021 Malian Nonuplets
The most prominent case of surviving nonuplets involved Halima Cissé, a Malian woman who gave birth to nine babies in Casablanca, Morocco, in May 2021. Cissé had been undergoing fertility treatment for difficulty conceiving. Ultrasounds during the pregnancy initially detected seven fetuses; two additional babies were discovered at delivery. All nine survived, setting a record for the most children born in a single delivery with all surviving past infancy.
Public reports indicated that Cissé’s treatment involved ovarian stimulation rather than IVF. The case drew international attention in part because pregnancies of this order are extraordinarily rare, and complete survival of all fetuses is rarer still. Previous known nonuplet pregnancies, such as cases reported in Australia in the 1970s and Malaysia in the 1990s, did not result in the survival of all nine infants. The Cissé case highlighted both the potential and the risks of fertility medication when the ovarian response exceeds expectations.
Why IVF Carries a Different Risk Profile
It might seem counterintuitive that IVF, often perceived as the more “aggressive” fertility intervention, actually gives clinicians more control over multiple pregnancies than simpler treatments do. The reason is straightforward: with IVF, eggs are collected before fertilization happens. Embryos are created in a laboratory, and a physician decides how many to place in the uterus. That decision point simply does not exist with ovarian stimulation plus intercourse or insemination.
An important advantage of IVF is precisely this ability to limit the number of embryos transferred. In many European countries, elective single-embryo transfer has become standard practice and has significantly reduced multiple pregnancy rates while keeping birth rates acceptable.1PubMed Central. In vitro fertilization and multiple pregnancies: an evidence-based analysis When the number of embryos transferred is not limited, though, IVF-associated multiple pregnancy rates look similar to those from other ovarian stimulation treatments. The critical variable is not the technology itself but whether anyone controls how many embryos get a chance to implant.
Single-embryo transfer does not eliminate multiples entirely. In a study of over 65,000 single-embryo transfers, roughly 2% of pregnancies still resulted in two or more heartbeats, because the single transferred embryo had split into identical twins or, rarely, triplets.2PubMed Central. Recurrence risk and risk factors for monozygotic twin and triplet birth in over 65,000 single-embryo transfers But that 2% figure is a long way from nonuplets. The pregnancies of extreme order, five or more fetuses, are almost exclusively the product of uncontrolled ovarian stimulation cycles.
How Monozygotic Splitting Adds to the Count
While ovarian stimulation primarily creates multiple pregnancies by releasing many separate eggs (each producing a fraternal sibling), monozygotic splitting can also contribute. A single fertilized egg sometimes divides into two or more genetically identical embryos. This process is not fully understood even in twin pregnancies, but research has identified physical forces during early embryo development that can cause the inner cell mass of a blastocyst to separate.3PubMed Central. Cellular mechanisms of monozygotic twinning: clues from assisted reproduction
In theory, a woman who releases seven eggs during an ovarian stimulation cycle could end up with nine fetuses if two of those fertilized eggs each split into identical pairs. This combination of fraternal multiples and identical splitting is one plausible explanation for how the count reaches nine. Clinicians monitoring a stimulated cycle with ultrasound can count developing follicles, but they cannot predict which fertilized eggs will split after conception. The splitting itself is a biological wild card that makes the final number of fetuses difficult to forecast even when the number of released eggs is known.
Monitoring and Cancellation of Risky Cycles
Responsible fertility clinics monitor stimulated cycles with serial ultrasounds and blood tests to count how many follicles are developing. When too many follicles mature, the standard recommendation is to cancel the cycle: withhold the ovulation trigger, advise the patient to avoid intercourse, or convert the cycle to IVF so that the number of embryos transferred can be controlled. The challenge is that “too many” is a judgment call, and patient compliance after leaving the clinic cannot be guaranteed. Some patients, understandably desperate after months or years of failed attempts, proceed with intercourse despite warnings.
The difficulty is compounded in healthcare settings with fewer resources for monitoring. Ovarian stimulation drugs are far less expensive than a full IVF cycle, so they are often used in contexts where repeated ultrasound monitoring is harder to access. This gap between the availability of fertility drugs and the availability of close monitoring is one of the structural reasons high-order multiple pregnancies still occur.
Health Risks for the Mother
Carrying nine fetuses places enormous physiological strain on the body. Research on triplet and higher-order pregnancies shows a dose-response pattern: the more fetuses, the higher the risk of serious complications. Compared with twin pregnancies, women carrying triplets and higher-order multiples face increased odds of pregnancy-associated hypertension, eclampsia, anemia, gestational diabetes, placental abruption, premature membrane rupture, and cesarean delivery.4PubMed. Maternal morbidity and obstetric complications in triplet pregnancies and quadruplet and higher-order multiple pregnancies A separate large study confirmed that multiple pregnancies significantly increase rates of anemia, preterm labor, gestational diabetes, hypertensive disorders, and postpartum hemorrhage.5PubMed Central. Maternal and neonatal outcomes in multiple pregnancy: A multicentre study in the Beijing population
With nonuplets, these risks scale to an extreme that has little precedent in the medical literature. The uterus is stretched far beyond its normal capacity, the blood volume required to supply nine placentas is massive, and the pregnancy almost inevitably ends in a very early preterm cesarean delivery. Halima Cissé delivered at around 30 weeks of gestation, which is remarkably late for a pregnancy of that order. The babies’ birth weights ranged from roughly 500 grams to 1 kilogram, placing all of them in the category of very low or extremely low birth weight.
Care Strategies for Extreme Multiples
Managing a pregnancy with five or more fetuses requires a highly specialized team. Guidelines for high-order multiples emphasize preterm birth prevention education, frequent assessment of maternal symptoms and cervical status, individualized activity modification, close attention to nutrition, and regular ultrasound for fetal anatomy and growth monitoring.6PubMed. Obstetric management of high-order multiple pregnancies Routine use of interventions like preventive cerclage, uterine activity monitoring, or automatic hospitalization has not consistently improved outcomes, so care tends to be tailored to the individual case rather than following a one-size-fits-all protocol.
One specific concern in any pregnancy that includes monozygotic siblings sharing a placenta is vascular anastomosis, where blood vessels connect between two fetuses through the shared placenta. This can lead to a condition resembling twin-to-twin transfusion syndrome, causing uneven growth between the affected pair.7Global Library of Women’s Medicine. Higher-Order Multiple Gestations In a nonuplet pregnancy, identifying which fetuses share a placenta and which have separate placentas is a critical early step, because it determines which complications the team needs to watch for most closely.
Fetal Reduction as a Clinical Option
When a fertility treatment produces a pregnancy with many more fetuses than can be safely carried to viability, fetal reduction is one of the options discussed with the patient. This procedure, typically performed between 11 and 14 weeks of gestation, involves an ultrasound-guided injection that stops the heart of one or more selected fetuses, reducing the pregnancy to a number more likely to result in healthy survivors.8Journal of Obstetrics, Gynecology and Cancer Research. Optimal Timing of Multifetal Pregnancy Reduction: The Earlier the Better or Later The selection is based on clinical factors: the position of the fetus, its nuchal translucency measurement, or detected abnormalities.
Fetal reduction improves the odds for the remaining fetuses by allowing the pregnancy to continue longer and the survivors to grow larger. But it carries its own risks, including a small chance of losing the entire pregnancy. In one hospital-based study, two pregnancy losses occurred before 24 weeks among the cases reviewed.9PubMed Central. Outcomes of Multifetal Reduction: A Hospital-Based Study The decision to reduce is deeply personal and ethically complex. In the case of the Malian nonuplets, the family chose not to pursue reduction, opting instead for intensive medical management throughout the pregnancy.
The Financial Weight of Multiple Births
The cost of delivering and caring for high-order multiples is staggering. Data from the United States shows that twin deliveries cost roughly five times as much as singleton deliveries, while triplet-and-higher deliveries cost nearly twenty times as much, with average adjusted costs exceeding $400,000 per delivery.10PubMed. Healthcare expenses associated with multiple vs singleton pregnancies in the United States These figures are driven largely by neonatal intensive care stays, which are almost universal for higher-order multiples. Extrapolating to nonuplets is speculative, but the costs would be extraordinary given nine simultaneous NICU admissions, many lasting months.
Beyond the direct medical bills, families with high-order multiples face long-term financial pressures. Insurance caps, the inability of families to cover all expenses out of pocket, and the burden on hospital systems all compound the problem.11PubMed. Less is more: the risks of multiple births In the Cissé case, the Malian government funded the family’s medical care in Morocco, an arrangement that underscored just how far beyond normal resources a nonuplet pregnancy falls.
Policy Efforts to Prevent Extreme Multiples
The reproductive medicine community has spent decades trying to reduce the incidence of high-order multiple pregnancies. For IVF, the most effective measure has been regulation or encouragement of single-embryo transfer. In Turkey, after regulations introduced in 2010, the multiple pregnancy rate from IVF dropped from about 38% to about 16%. Among patients under 35 who received a single blastocyst transfer, the multiple pregnancy rate fell to under 2%, with no significant drop in overall clinical pregnancy rates.12PubMed Central. Incidence of multiple births in relation to current regulations in Turkey regarding embryo transfer
In donor-egg IVF cycles in the United States, the multiple pregnancy rate exceeded 40% when more than one blastocyst was transferred, but plummeted to between 1% and 3% with single-embryo transfer.13PubMed Central. Reduction in multiple pregnancy rate in donor oocyte-recipient gestational carrier (GC) in vitro fertilization (IVF) cycles in the USA with single-embryo transfer and preimplantation genetic testing Single-embryo transfer has emerged as the key strategy for safe assisted reproduction, supported by counseling, health policy, and economic incentives.14PubMed Central. Single-embryo transfer: a key strategy to reduce the risk for multiple pregnancy in assisted human reproduction
The harder problem is ovarian stimulation cycles that do not involve IVF, since no embryo-transfer step exists where a clinician can intervene. Policies in these cases focus on stricter monitoring, lower starting doses, and clear cancellation criteria when too many follicles develop. But adoption varies widely across countries depending on clinical practice, healthcare funding, and patient expectations.15PubMed. Why are multiple pregnancy rates and single embryo transfer rates so different globally, and what do we do about it? This unevenness is part of why extreme higher-order multiples, while increasingly rare, have not disappeared entirely.
The Psychological Toll on Families
Even with twin pregnancies conceived through assisted reproduction, parents report heightened symptoms of depression, anxiety, and parenting stress compared to parents of singletons.16PubMed Central. Raising multiples: mental health of mothers and fathers in early parenthood Research on families with children born through fertility treatment found that parenting stress scores were significantly higher and depression scores were worse among parents of twins and multiples than among those with singletons.17PubMed Central. Families with children resulting from ART: psychosocial and financial implications
These findings come from studies of twins and triplets. For a family with nine infants arriving at once, the logistical and emotional demands are on a different scale entirely. Sleep deprivation is relentless, feeding schedules dominate every hour, and the sheer physical labor of caring for nine babies requires multiple caregivers around the clock. Families who have navigated high-order multiples often describe the early years as a blur of exhaustion and logistical problem-solving, punctuated by genuine joy but also serious strain on parental relationships and mental health.
How Media Coverage Shapes Perception
High-order multiple births reliably generate intense media interest, and the coverage tends to lean heavily toward celebration. Journalists portray the families as miraculous and resilient, which is understandable but can distort public understanding of the medical reality. One review found that only about 8% of articles about a well-known septuplet birth in the United States criticized the parents’ decision, even though the fetal risks involved in very-high-order multiple pregnancies are severe.18Newborn and Infant Nursing Reviews. Review Ethical Issues of High-order Multiple Births
The result is a gap between the public narrative and the clinical one. Viewers see healthy babies going home and understandably conclude that the outcome was happy. What they do not see is the months of NICU care, the long-term developmental monitoring, the financial strain, or the pregnancies of similar order that ended in loss. When media coverage makes extreme multiples look like a feel-good story with a guaranteed happy ending, it can also make it harder for reproductive medicine professionals to have honest conversations with patients about the risks of aggressive fertility treatment. The medical community’s position is clear: pregnancies of this magnitude represent an outcome to be prevented, not celebrated, even when the babies survive.