Assisted reproductive techniques are associated with a higher incidence of hypertensive disorders of pregnancy, partly explained by multiple gestations, advanced maternal age, comorbidities, cause of infertility, and ovarian hyperstimulation syndrome [16, 17]. Kidney impairment can be expected to be common in such a setting, considering its association with lower fertility rates, but may go unreported, particularly in medium–low resource settings, due to a lack of awareness of the importance of kidney function tests and absence of screening protocols.

The present study reports six cases of severe proteinuria, with hypertension and kidney function impairment occurring after different assisted reproductive technology procedures, five in the context of early-onset hypertensive disorders of pregnancy, and one with acute kidney injury. This series exemplifies threatening situations that could, at least in part, be prevented, and whose risk should be considered and explained before women begin assisted reproductive technology procedures.

Only one of our patients had undergone kidney function tests before assisted reproductive technology, and a history of previous kidney disease (biopsy-proven FSGS) was overlooked in one patient (case 3); CKD may have been present in another patient (case 4) who was, however, lost to follow-up before diagnosis was completed. Conversely, in case 5 a diagnosis of pelvic kidney was made, which should have led to stricter follow-up during pregnancy, for the well-known association between all renal alterations, including interstitial diseases, and higher risk of adverse pregnancy outcomes [18]. While kidney function assessment prior to assisted reproductive technology is not mandatory, some authors hold that kidney function assessment should be considered in all pregnancies [19, 20] or at least in high-risk situations, including assisted reproductive technology (the 2023 KDIGO Conference in Athens). None of our patients had been referred for preconception counseling, and a measure of the lack of information that exists can also be seen in the difficulty we had in retrieving information on their medical histories, treatments and procedures (Table 1).

The most important finding in this series is the early timing of onset of proteinuria and hypertension, occurring before the classic term of 20 gestational weeks, identified as diagnosing hypertensive disorders of pregnancy. While exceptions exist, and some have been reported, especially in multiple pregnancies or after oocyte donation, to date this is the largest series reporting on severe kidney involvement after assisted reproductive technology, in the context of conjoint nephrology and obstetric management [21, 22]. Interestingly, only three of our cases were twin pregnancies and none had undergone oocyte donation. A recent systematic review, published in 2023 [23], reported on 37 cases of early-onset preeclampsia, only 10% of which ended in live births. In this series, 6 were multiple pregnancies, 9 partial or complete molar pregnancies, and the use of an assisted reproductive technology was reported in 3 cases (two egg donations). Of note, in 7 cases reported in this review anti-phospholipid antibodies were present, indicating the close relationship between pregnancy and autoimmune and kidney diseases, and the difficulties encountered in diagnosing hypertensive disorders of pregnancy in these settings [23].

The diagnosis of hypertensive disorders of pregnancy is clinical and is supported by at least initial improvement in the 5 cases followed up after delivery, with full remission in three. The availability of placental biomarkers, that were however tested in only one case, and outside our country, could help in these situations by supporting a differential diagnosis between CKD and preeclampsia. This highlights how low availability of diagnostic tools (and potential treatments) is a barrier that needs to be overcome in low-medium income countries and underlines that kidney involvement needs to be given greater attention. Likewise, an important limitation is that information on our cases was often incomplete, an issue that is shared by the studies done in developing countries, in particular when private medicine is involved.

A further important suggestion comes from the observation that in our series only one woman was undergoing assisted reproductive technology for the first time, while the other five had undergone as many as 7 previous attempts of assisted fertilization. Within the limits of our report, this suggests that greater attention should be paid to kidney function in women who have undergone several assisted reproductive technology cycles, an issue as yet unexplored.

Caring for these patients poses not only clinical, but also ethical questions, that remain, for the moment, unsolved. None of the women we describe had a living child, although all of them had been married for several years, and they all desperately wanted to give birth. We have no data that would allow us to advise them against trying to conceive again, even if our experience on the recurrence of hypertensive disorders of pregnancy supports concerns for their kidney function and overall health, should they once more undergo assisted reproductive technology [24,25,26].

In conclusion, kidney dysfunction is a potential, possibly underreported complication, after assisted reproductive technology protocols, especially if repeated and if performed outside carefully monitored situations.

The association between assisted reproductive technology and early onset hypertensive disorders of pregnancy remains an area requiring further investigation as published data are insufficient to explore this association and well-designed future studies are needed to further elucidate our observation.

Especially in low-medium income countries, in which cultural pressure to have large families is strong, and being childless may be seen as a stigma, the risks connected with assisted reproductive technology can be particularly challenging. Better care, more resources, and better health education are still unmet needs. Health equity still has a long way to go when pregnancy is concerned.